Cost-effectiveness of talazoparib plus enzalutamide as first-line therapy in metastatic castration-resistant prostate cancer

Cost-effectiveness of talazoparib plus enzalutamide as first-line therapy in metastatic castration-resistant prostate cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cost-effectiveness of talazoparib plus enzalutamide as first-line therapy in metastatic castration-resistant prostate cancer Jiaming Zhu, Zhengxiong Li, Ye Ding, Qiaoping Xu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6199993/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The TALAPRO-2 trial demonstrated that the combination of talazoparib and enzalutamide significantly improved both progression-free survival (PFS) and overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, the cost-effectiveness of this regimen remains unclear due to its high cost. This study aims to evaluate the cost-effectiveness of this combination compared to enzalutamide monotherapy as a first-line treatment for mCRPC. Methods Based on data from the TALAPRO-2 trial, a dynamic Markov model was constructed to simulate disease progression in mCRPC patients. From the perspectives of US and Chinese payers, total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER) were considered as the primary outputs in the model. One-way sensitivity analysis and probabilistic sensitivity analysis were used to validate the robustness of the model. Price reduction analysis provides an evidence-based basis for drug pricing and health insurance negotiations by quantifying the impact of price adjustments on economics. Results In the baseline analysis, the ICERs for talazoparib plus enzalutamide were $ 646,743.72/QALY and $ 57,635.76/QALY from the U.S. and China perspectives, respectively, which were above the willingness-to-pay thresholds ( $ 150,000 in the U.S. and $ 40,334 in China). Sensitivity analyses showed that PFS utility values and drug prices impacted the results most. Price adjustment scenarios showed that China needed a 34.5% price reduction to achieve affordability, whereas the U.S. remained unaffordable even with an 80% price reduction. Conclusion At current pricing, talazoparib plus enzalutamide is not cost-effective for mCRPC patients. Optimizing its economic viability may be possible through genetic testing to screen for HRR mutation-positive populations or price negotiations to reduce drug costs. The study supports differentiated pricing strategies to balance clinical benefits with the rational allocation of healthcare resources. metastatic castration-resistant prostate cancer Markov model talazoparib enzalutamide cost-effectiveness Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Accounting for nearly one-tenth of cancer mortality in American men, prostate cancer represents the second leading cause of male cancer incidence nationwide.[ 1 ]. This mortality burden is primarily attributed to its high propensity for bone metastasis and the eventual failure of hormonal therapies. The proliferation of early-stage prostate cancer critically depends on androgen receptor (AR) signaling and its ligand testosterone, which has prompted the development of therapeutic strategies targeting both androgen biosynthesis and AR-mediated oncogenic pathways. Androgen deprivation therapy (ADT), encompassing surgical castration and pharmacologic approaches, aims to suppress systemic androgen synthesis. However, a subset of patients exhibit disease progression post-ADT through AR overexpression that sustains tumor growth in low-testosterone environments[ 2 , 3 ], leading to metastatic castration-resistant prostate cancer (mCRPC). To address this, second-generation AR competitive inhibitors including enzalutamide, apalutamide[ 4 ] and androgen precursor synthesis inhibitors like abiraterone acetate have been employed in mCRPC management, demonstrating significant clinical benefits in multiple Phase III trials[ 5 , 6 ]. Nearly one-third of individuals diagnosed with prostate cancer present with genetic alterations in DNA damage repair (DDR) pathways, predominantly involving homologous recombination repair (HRR)-associated genes. The HRR pathway encompasses multiple members including ATM, CHEK2, and BRCA1/2. An observational study demonstrated that patients with HRR mutations (HRRm) exhibited shorter overall survival and differential therapeutic responses to identical treatment modalities compared to non-HRRm counterparts[ 7 ]. Consequently, ctDNA genomic profiling to delineate molecular characteristics enables optimized therapeutic decision-making and prognostic evaluation[ 8 ] Poly(ADP-ribose) polymerase (PARP), a critical enzyme in DNA damage repair, demonstrates enhanced activity mediated by AR inhibition during ADT, concomitant with downregulation of HRR gene expression. Given the high prevalence of homologous recombination repair deficiency in metastatic mCRPC, PARP inhibitors exert synthetic lethality by impairing DNA repair mechanisms, particularly when combined with ADT, thereby conferring survival benefits in advanced mCRPC. Recent phase III trials including PROfound and PROpel established that olaparib combined with abiraterone significantly prolongs progression free survival (PFS) and overall survival (OS) across all study populations, with enhanced clinical benefits observed in HRRm and BRCA1/2-mutated cohorts. This regimen has been endorsed as a Category 1A recommendation for mCRPC treatment in the 2024 American Society of Clinical Oncology (ASCO) guidelines. Subgroup analyses revealed striking efficacy differences: HRRm subgroups achieved rPFS HR = 0.66 versus HR = 0.89 in non-HRRm groups, with BRCA1/2-mutated cohorts demonstrating HR = 0.29. These findings were corroborated in the PROfound cohort[ 9 , 10 ]. Olaparib and rucaparib have received US and Europe approval as first-line therapies for mCRPC patients with BRAC1/ 2mutations[ 9 , 11 ]. A majority of experts consensus strongly supports PARP inhibitor (PARPi) combination therapy with androgen receptor pathway inhibitors in BRCA1/2-altered patients, while demonstrating overwhelming opposition to PARP inhibitor use in DDR-intact mCRPC cases. Current treatment algorithms recommend referencing mHSPC therapeutic paradigms for DDR-wildtype mCRPC management[ 12 ]. In 2018, talazoparib received FDA approval for prostate cancer treatment and was subsequently designated as a first-line therapeutic agent for mCRPC by the Chinese Society of Clinical Oncology (CSCO) guidelines in 2020. The phase III TALAPRO-2 trial demonstrated that talazoparib plus enzalutamide significantly improved PFS and OS across the entire study population, achieving a 37% reduction in risk of disease progression or death (HR = 0.62; 95% CI 0.475–0.814).Subgroup analyses stratified by HRR gene mutation status revealed substantial therapeutic heterogeneity: the talazoparib plus enzalutamide cohort with HRRm exhibited median OS not reached after 52.5 months of follow-up, compared to 42.4 months in non-HRRm patients receiving the same combination. This underscores the critical impact of HRR mutational status on clinical outcomes with talazoparib based therapy. Notably, this study provides pivotal evidence that HRR mutation profiling constitutes a more robust predictor of therapeutic responsiveness to PARP inhibitor-ADT combination regimens than BRCA1/2 mutation status alone. (ASCO GU; February 13–15, 2025). Although the combination therapy of talazoparib and enzalutamide has demonstrated clinical efficacy in the TALAPRO-2 trial, its high cost compared to other PARP inhibitors[ 13 ] raises uncertainties regarding the cost-effectiveness of global implementation, particularly in middle-income countries where its potential to improve quality of life for mCRPC patients remains unverified. To optimize healthcare resource allocation, identify high-benefit patient subgroups, enhance scientific decision-making in treatment strategies and drug pricing, and balance multi-stakeholder interests, this study evaluates the cost-effectiveness of talazoparib plus enzalutamide versus enzalutamide monotherapy from the perspectives of U.S. and Chinese healthcare payers. 2. Materials and methods 2.1 Population and intervention This research strictly adhered to the updated Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022). Detailed compliance with each checklist item is provided in Additional file Table S1 . Based on the TALAPRO-2 clinical trial, the model simulated mCRPC patients aged 70 years (the median age of the clinical trial population) who had received continuous castration therapy (testosterone ≤ 50 ng/dL) with ongoing ADT, presented radiologically confirmed bone or soft tissue metastases, and exhibited asymptomatic or mildly symptomatic disease. The target patient population was randomly assigned 1:1 to either the TALA arm or the placebo (PBO) group. The TALA arm received two 0.25 mg talazoparib capsules administered orally once daily plus four 40 mg enzalutamide capsules daily, while the PBO arm received two matching placebo capsules daily alongside four 40 mg enzalutamide capsules. Upon radiographically confirmed disease progression, second-line therapeutic regimens from the TALAPRO-2 supplementary appendix were initiated, with remaining progressive cases receiving best supportive care. Monitoring protocols followed the TALAPRO-2 study design during the initial 56 weeks of follow-up, transitioning thereafter to surveillance strategies recommended by the CSCO guidelines. Patients continued treatment until death, adverse event-induced discontinuation, or study endpoint attainment. 2.2 Model construction This study employed a dynamic Markov model constructed using TreeAge Pro 2022 software (TreeAge, Williamstown, MA) to evaluate the cost-effectiveness of talazoparib plus enzalutamide in treating mCRPC. Within the modeling framework, patients could transition between three mutually exclusive states: PFS, progressive disease (PD), and the absorbing state of death. As per model specifications, the initial health state for the entire cohort was defined as PFS and could transition between these states during disease progression. (Fig. 1 ) A 28-day cycle length was implemented to align with TALAPRO-2 treatment intervals, with a 30-year time horizon to sufficiently capture mortality events. The economic evaluation focused on three principal endpoints: total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). All cost and utility estimates underwent 3% and 5% annual discounting in US and China with half-cycle correction. Following the 2020 Chinese Pharmacoeconomic Evaluation Guidelines[ 14 ], willingness-to-pay (WTP) thresholds were set at $ 40,334 (3×China′s 2024 per capita GDP) for China and $ 150,000 for the U.S.[ 15 ]. 2.3 Clinical data Given the unavailability of original individual patient data (IPD), OS and PFS estimates for the mCRPC cohort were derived from Kaplan-Meier (KM) curves published in the TALAPRO-2 trial. For quantitative analysis of published survival data, the GetData Graph Digitizer platform (Version 2.26) was employed to capture data points from both OS and PFS curves published by TALAPRO-2 experiment, and R software (Version 4.3.2) was used to reconstruct IPD. Based on Guyot et al.’s[ 16 ] algorithm, Exponential, Weibull, Log-logistic, Log-normal, and Gompertz standard parametric survival functions were subsequently employed to fit and extrapolate survival curves. The final model selection was determined through a comprehensive evaluation incorporating Akakike Information Criterion (AIC) and Bayesian Information Criterion (BIC) statistical criteria, complemented by graphical assessment.(Additional file: Table S2 and Figure S1 ) The optimal distributions for OS and PFS survival curves were Log-logistic \(\:\text{S}\left(\text{t}\right)=\frac{1}{1+{\left({\lambda\:}t\right)}^{{\gamma\:}}}\) and Log-normal \(\:S\left(t\right)=1-{\Phi\:}\left(\frac{\text{ln}t-{\mu\:}}{{\sigma\:}}\right)\) , fitting OS and PFS survival curves for talazoparib plus enzalutamide and placebo plus enzalutamide, respectively. Detailed fitting results can be found in the (Additional file: Table S3 and Figure S2). 2.4 Transition probability The disease progression dynamics in mCRPC patients were simulated using transition probability modeling, which incorporated the method of Latime et al.[ 17 ] to calculate time-dependent transition probabilities between distinct health states within Markov models. (Additional file: Table S4) The transition probability from PFS to death was assumed to be the natural mortality. Based on OS and PFS survival functions, the specific-cycle transition probability between states was calculated using the following formula: \(\:\text{t}\text{p}\left({\mu\:}\right)=1-\frac{\text{S}\left(\text{t}\right)}{\text{S}\left(\text{t}-{\mu\:}\right)}\) where µ is the cycle length. 2.5 Cost and utility This study adopts the perspectives of third-party payers in China and the U.S., considering only direct medical costs, which include first-line treatment drug costs, second-line treatment costs after disease progression, examination costs, follow-up costs, hospice care costs, and the treatment costs of the top five severe adverse events (AEs) (grade ≥ 3). (Table 1 ) The price adjustments were made using the consumer price index (CPI) to reflect inflation, and all costs were adjusted to the 2025 US dollars according to the formula from https://www.infationtool.com . Since second-line treatments such as Cabazitaxel and Doxitaxel require dosing based on patient body surface area, we assume the average weight of US and Chinese patients to be 70 kg and 65 kg, respectively, to calculate dosing and costs, which are then incorporated into sensitivity analysis. As Lutetium is not yet available in China, its cost in China is estimated by multiplying the US cost by the ratio of talazoparib costs in China and the US. Other costs are obtained from local tertiary hospital fee standards, published literature, and relevant websites, and all second-line treatment costs are weighted before being input into the model. (Table 2 ) Table 1 Clinical outcomes for each cohort Parameter Talazoparib plus enzalutamide Placebo plus enzalutamide Risk of grade3 ~ 5 AEs (%) Total AEs 75.13 45.14 Anaemia 46.48 4.23 Neutropenia 18.34 1.50 Thrombocytopenia 7.29 1.00 Hypertension 5.28 7.48 Fatigue 4.02 2.00 Proportion receiving second-line treatment (%) 18.84 11.22 Docetaxel 16.58 26.68 Cabazitaxel 6.03 11.47 Abiraterone plus prednisone 7.29 12.22 Olaparib 0.75 2.74 Lutetium 0.50 2.00 Radium 2.76 4.74 BSC 66.08 40.15 AEs: Adverse events, BSC: Best supportive care Table 2 Cost in US and China Input Parameter Baseline SA range Distribution Ref. Baseline SA range Distribution Reference US China Price of drug Price of talazoparib per 0.25 mg 510.49 408.39 ~ 612.59 Gamma yaozh.com 71.68 57.34 ~ 86.02 Gamma hospital charge Price of talazoparib per cycle 28587.16 22869.73 ~ 34304.59 Gamma yaozh.com 4014.08 3211.26 ~ 4816.90 Gamma hospital charge Price of enzalutamide per 40 mg 125.08 100.06 ~ 150.10 Gamma [ 23 ] 6.60 5.28 ~ 7.92 Gamma yaozh.com Price of enzalutamide per cycle 15072.26 12057.81 ~ 18086.71 Gamma [ 23 ] 739.20 591.36 ~ 887.04 Gamma yaozh.com Cost of second-line treatment per cycle Docetaxel 2228.95 1783.16 ~ 2674.74 Gamma [ 23 ] 961.46 769.17 ~ 1153.75 Gamma [ 23 ] Cabazitaxel 11989.47 9591.58 ~ 14387.36 Gamma [ 30 ] 1642.3592 1313.89 ~ 1970.83 Gamma selleck.cn Abiraterone plus prednisone 12457.62 9966.10 ~ 14949.14 Gamma [ 23 ] 638.9923 511.19 ~ 766.79 Gamma [ 23 ] Olaparib 16022.84 12818.27 ~ 19227.41 Gamma [ 23 ] 1820.68 1456.54 ~ 2184.82 Gamma [ 23 ] Lutetium 30628.29 24502.63 ~ 36753.95 Gamma [ 31 ] 4594.24 3675.39 ~ 5513.09 Gamma * Radium 13906.20 11124.96 ~ 16687.44 Gamma [ 32 ] 20,488.61 16390.89 ~ 24586.33 Gamma [ 33 ] Cost of monitoring per unit PSA 27.19 21.75 ~ 32.63 Gamma [ 34 ] 7.56 6.05 ~ 9.07 Gamma [ 35 ] CT 972.62 778.10 ~ 1167.14 Gamma [ 30 ] 230.10 184.08 ~ 276.12 Gamma [ 35 ] Bone scanning 275.67 220.53 ~ 330.80 Gamma [ 34 ] 153.35 122.68 ~ 184.02 Gamma [ 35 ] Laboratory examination 82.66 66.13 ~ 99.19 Gamma [ 34 ] 33.37 26.69 ~ 40.04 Gamma [ 35 ] Circulating tumour cell enumeration 937.00 749.60 ~ 1124.40 Gamma Fairhealthconsumer.org 431.00 344.80 ~ 517.20 Gamma RED BOOK Cost of BSC per cycle 1319.28 1055.42 ~ 1583.14 Gamma [ 34 ] 77.55 62.04 ~ 93.06 Gamma [ 34 ] Cost of terminal care 100908.12 80726.50 ~ 121089.74 Gamma [ 34 ] 2288.24 1830.59 ~ 2745.89 Gamma [ 34 ] Cost of follow up of per unit 458.98 367.18 ~ 550.78 Gamma [ 34 ] 56.01 44.81 ~ 67.22 Gamma [ 34 ] Cost of managing AEs (grade > 3) per event Anemia 1233.36 986.69 ~ 1480.03 Gamma [ 23 ] 579.70 463.76 ~ 695.64 Gamma [ 23 ] Neutropenia 29643.23 23714.58 ~ 35571.88 Gamma [ 36 ] 63.99 51.20 ~ 76.79 Gamma [ 37 ] Thrombocytopenia 2487.64 1990.11 ~ 2985.17 Gamma [ 36 ] 598.85 479.08 ~ 718.62 Gamma [ 37 ] Hypertension 2637.46 2109.97 ~ 3164.95 Gamma [ 36 ] 16.81 13.45 ~ 20.17 Gamma [ 37 ] Fatigue 10721.77 8577.42 ~ 12866.12 Gamma [ 23 ] 88.64 70.91 ~ 106.37 Gamma [ 23 ] Discount rate 0.03 0 ~ 0.08 Fix [ 38 ] 0.05 0 ~ 0.08 Fix [ 38 ] Body surface 1.84 1.74 ~ 2.21 Gamma [ 35 ] 1.72 1.38 ~ 2.96 Gamma [ 35 ] SA: Sensitivity analysis PSA: Prostate specific antigen, CT: Computed tomography, AE: Adverse event, BSC: Best supportive care, *Since Lutetium is not approved in China, its cost in the Chinese context was estimated based on the US market price, with the cost conversion ratio referenced to the price differential of Talazoparib between China and the United States Utility values, ranging between 0 and 1, measure patients' quality of life and indirectly reflect the benefits of medical interventions. The utility values for PFS and PD states are obtained from relevant literature, while the utility decrements due to AEs include only the disutility values of the top five AEs with grade ≥ 3 severity. (Table 3 ) Table 3 Utility and disutility in model Health utility Baseline SA range Distribution Reference Progressive disease 0.65 0.52 ~ 0.78 Beta [ 25 ] Progression-free survival 0.76 0.61 ~ 0.91 Beta [ 25 ] Disutility Anemia 0.11 0.09 ~ 0.13 Beta [ 39 ] Neutropenia 0.1 0.08 ~ 0.12 Beta [ 39 ] Fatigue 0.47 0.38 ~ 0.56 Beta [ 39 ] 2.6 Sensitivity analysis We used one-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) to explore the impact of each variable input into the model on the ICER. In the OWSA, the low and high values of each variable were determined by ± 20% of the baseline value, with the high value of the discount rate set at 0.8 and the low value at 0. The results of the OWSA were presented using Tornado diagram. Additionally, we conducted 10,000 Monte Carlo simulations for the PSA, assuming that the costs in the model followed a Gamma distribution, while utility values, AE rates, and the proportion of second-line treatment choices were assumed to follow a Beta distribution. The results of the PSA were presented in the form of cost-effectiveness acceptability curves and ICER scatterplots. 2.7 Scenario analysis To further explore the cost-effectiveness of talazoparib plus enzalutamide in the treatment of mCRPC, we conducted a price reduction simulation for talazoparib, assuming price reductions of 20%, 40%, 60%, and 80%, respectively. The analysis compared changes in the ICER and the probability of cost-effectiveness acceptability. 3. Result 3.1 Base-case analysis The results of the cost-effectiveness analysis showed that in the Chinese perspective, the total cost of treatment with talazoparib in combination with enzalutamide for mCRPC patients was $ 97,286, which amounted to an incremental cost of $ 53,537 compared to the total cost of $ 43,748 for treatment with enzalutamide. Compared to the enzalutamide-treated group that averaged or gained 2.25 QALYs, the talazoparib in combination with enzalutamide group could gain an additional 0.93 QALYs with an ICER of $ 57,635.76/QALY, which was greater than the Chinese payer WTP, suggesting that talazoparib in combination with enzalutamide was not economical. In the U.S. perspective, the incremental cost of the talazoparib plus enzalutamide group was $ 708,234, and its incremental utility and ICER were 1.1 QALYs and $ 646,743.72/QALY, respectively. From the Chinese perspective, the total cost of talazoparib plus enzalutamide was $ 97,286, which was $ 53,537 higher than enzalutamide monotherapy. Its ICER of $ 57,635.76/QALY was much higher than the Chinese payer threshold ( $ 40,334/QALY), suggesting that this combination regimen is not cost-effective in China. (Table 4 , Fig. 2 ) Table 4 Result of base-case analysis Strategy US China Total cost ( $ ) IC ( $ ) QALYs IE ICER ( $ /QALY) Total costs ( $ ) IC ( $ ) QALYs IE ICER ( $ /QALY) PBO + ENZA 532634.03 - 2.40 - - 43748.43 - 2.25 - - TALA + ENZA 1240867.98 708233.95 3.49 1.10 646743.72 97285.24 53536.81 3.18 0.93 57635.76 IC: Incremental Cost, IE: Incremental Effectiveness, ICER: Incremental Cost-Effectiveness Ratio, QALYs: Quality-Adjusted Life Years, PBO: Placebo, TALA: Talazoparib, ENZA: Enzalutamide 3.2 Sensitivity analysis OWSA showed that the most influential parameter on ICER in both the US and Chinese perspectives was the utility of PFS state. Of the remaining parameters entered into the model, those that had a greater impact on the ICER values were the unit price of talazoparib, the unit price of enzalutamide, and the utility of PD state, respectively. Changes in other variables had less impact on the stability of the model, showing that the model is stable and the conclusions of this study are reliable, all parameters of in the range of changes cannot make the ICER value lower than the WTP. (Fig. 3 ) PSA of the scatterplot shows that all scatters fall above the WTP line, (Fig. 4 ) that is, none of the treatment of razoparib in combination with enzalutamide is economical compared with enzalutamide alone, the Chinese threshold value of $ 40,334 when accepting the proportion of 1.33%, and 0% acceptance at a WTP of $ 150,000 in the U.S. 3.3 Scenario analysis After doing 20%, 40%, 60%, and 80% price reductions for talazoparib 0.25 mg unit price, it was found that the talazoparib plus enzalutamide group demonstrated economy with an acceptable probability of 64.87% for the Chinese payer perspective with a price reduction ratio of 40%. For the U.S. payer perspective, on the other hand, even with a price reduction percentage of 80%, talazoparib still did not demonstrate economy, resulting in talazoparib not demonstrating economy. Further study found that in the Chinese payer perspective, the talazoparib plus enzalutamide group showed higher economy when the price reduction percentage reached 34.5%. (Table 5 and Fig. 5 ) Table 5 Result of scenario analysis Reduction rate US China Adjusted ICER Reduction ratio of ICER Acceptability Adjusted ICER Reduction ratio of ICER Acceptability 20% 577605.24 10.69% 0% 47208.45 18.09% 18.64% 40% 508466.75 21.38% 0% 36781.14 36.18% 69.43% 60% 439328.26 32.07% 0% 26353.83 54.28% 97.28% 80% 370189.78 42.76% 0% 15926.52 72.37% 99.96% ICER: Incremental cost-effectiveness ratio 4. Discussion Prostate cancer is a malignancy with persistently high incidence in males. Following ADT treatment, patients may transition from hormone-sensitive to castration-resistant status, indicating tumor androgen independence and failure of castration therapy. The HRR gene-deficient cells experience a functional impairment in their DNA double-strand break repair mechanisms. [ 18 ]. Since the proposal of the concept that PARPi induce synthetic lethality in HRR-deficient tumor cells by blocking the backup DNA repair pathway[ 19 ] first-generation PARP inhibitors such as olaparib and talazoparib have been developed and entered clinical trials. The TALAPRO-2 trial investigated the clinical significance of talazoparib plus enzalutamide in mCRPC populations. Results showed that talazoparib extended patient OS by 14 months and PFS by 18.4 months. In January 2024, the European Commission granted regulatory approval for the talazoparib-enzalutamide combination therapy in the management of mCRPC without clinical indications for chemotherapy, marking the first PARPi regimen certified by the European Commission. A network meta-analysis indicated that, compared with other PARPi combined with AR signaling inhibitor therapies, talazoparib plus enzalutamide holds the greatest potential to prolong PFS, thereby reducing the need for second-line treatments [ 20 ]. However, the high cost of talazoparib limits its economic viability and clinical application. This investigation represents, to our knowledge, the inaugural economic evaluation of talazoparib-enzalutamide combination therapy as a first-line treatment for mCRPC, incorporating both Chinese and U.S. healthcare perspectives. From the Chinese and U.S. perspectives, the cost of talazoparib plus enzalutamide significantly exceeded that of enzalutamide monotherapy, with incremental costs per additional QALYs gained reaching $ 57,635.76 and $ 646,743.72 respectively, both surpassing our pre-defined WTP thresholds. Consequently, the combination therapy lacks economic feasibility in both countries. Univariate sensitivity analysis revealed that key drivers of ICER in both contexts were utility values during PFS, drug prices of talazoparib and enzalutamide, utility values during PD, and discount rates. This highlights the critical impact of scientific drug pricing on the acceptability of this regimen. The pronounced influence of PFS utility values on ICER suggests that selecting patients with HRR gene mutations for talazoparib plus enzalutamide therapy could extend PFS duration, thereby increasing QALYs and reducing ICER. This supports the necessity of HRR gene testing at diagnosis. Price reduction simulations for talazoparib demonstrated that a 20% price cut in China reduced ICER to $ 47,208.45, increasing cost-effectiveness acceptability probability from < 1–15%, indicating that moderate price adjustments could substantially improve economic viability—a finding particularly relevant given talazoparib’s high pricing in China. At 40% price reduction, the combination therapy demonstrated superior cost-effectiveness versus enzalutamide monotherapy. Further analysis showed that a 34.5% price reduction achieved 50% cost-effectiveness probability. In China, drug pricing is closely tied to national medical insurance inclusion, and future centralized procurement/price negotiations could reasonably bring ICER within acceptable ranges. In the U.S. perspective, we found that even with an 80% price reduction for talazoparib, the benefit of gaining one additional QALYs when the WTP is $ 150,000 still does not cover the incremental cost of $ 370,189.78. And for every 20% price reduction of talazoparib, the ICER value was only reduced by 10.69%, suggesting that the high cost of other adverse effect management and second-line treatment is also one of the reasons why talazoparib in combination with enzalutamide does not show economy. On the one hand, the U.S. has a high degree of drug marketization, and the price of PARPi drugs such as talazoparib fluctuates with patent expiration and extensive development of PARP inhibitors; On the other hand, PARP inhibitors have shown clinical benefits in malignant tumors such as breast cancer [ 21 ] the expansion of market capacity may lead to increased competition in the market, further driving the price of talazoparib back down. Currently, the higher price of talazoparib is not reflective of its true value to U.S. payers, and we expect that talazoparib will achieve efficacy-based pricing to reduce payer risk. The sensitivity of the model to talazoparib demonstrates that there are price distortions in the current price of talazoparib, likely due to patent protection and market monopoly, and that reasonable price reductions and differentiated pricing based on regional levels of development could correct the price distortions and improve the economics of talazoparib in combination with enzalutamide. Data from the TALAPRO-2 trial showed that the combination therapy reduced the risk of progression of the disease by 37% but the price would need to be commensurate with the health benefit in order to maximize its health-promoting effect. Fortunately, Pfizer runs a patient assistance program that makes lower-cost treatment with talazoparib available to some low- and middle-income populations. The PROpel trial, conducted concurrently with TALAPRO-2, explored the clinical efficacy of olaparib in combination with abiraterone in patients with mCRPC. Olaparib as approved by the FDA as a treatment for mCRPC patients with BRAC mutations [ 22 ], shows very different results in the study of Xu et al[ 23 ]. They found that olaparib in combination with abiraterone was also not economical in China, which is consistent with our opinion, whereas in the US perspective, the cost of the olaparib plus abiraterone treatment group was instead decreased by $ 69,675.20 compared to the control group and higher utility values were obtained (incremental effectiveness = 0.23), which is undoubtedly economical in the US perspective. There are several reasons for this difference.1) Olaparib costs $ 17,313.88 for a treatment cycle in the U.S. market after discounting to 2025 dollars, which is only 60% of the cost of talazoparib over a treatment cycle, making it more economical;2)Xu et al.'s data were derived from the PROfound cohort[ 9 ], which exclusively enrolled mCRPC patients with BRCA1/2 or ATM defects. In contrast, the TALAPRO-2 cohort included an all-comer population regardless of HRR gene mutation status. Our study simulated the cost-effectiveness of talazoparib plus enzalutamide in this unselected population, where the incremental benefits were understandably lower than in populations with PARP inhibitor-targetable genetic alterations. This indirectly indicates that while olaparib demonstrates better economic viability in the U.S., its target population is narrower than talazoparib's. The cost-effectiveness of olaparib in genetically unselected broad populations remains uncertain. 3) The PROfound trial reported substantially fewerAEs than the TALAPRO-2 trial. In the olaparib-abiraterone treatment arm, the incidence of grade ≥ 3 overall AEs and grade ≥ 3 anemia was 51% and 21% respectively, compared to 75% and 46% in the talazoparib plus enzalutamide arm. Combined with the 19-fold higher cost of AEs management per treatment cycle in the U.S. versus China, these factors led to lower total costs for olaparib plus abiraterone therapy. Consequently, its ICER against the comparator was more favorable, thereby demonstrating economic viability. Srinivas et al[ 24 ] conducted a cost-effectiveness analysis of olaparib combined with abiraterone for BRCA1/2-mutated mCRPC patients from an Australian perspective. The results showed an incremental cost of $ 4884.141 for an additional 0.06QLAYs yielding an ICERof $ 91138/QALY, At Australia's defined WTP threshold of $ 62,289.772, this regimen was not cost-effective. Price reduction analysis revealed that a 30% reduction in olaparib's monotherapy price was required to achieve > 50% probability of cost-effectiveness acceptability for the olaparib plus enzalutamide. In conclusion, both talazoparib plus enzalutamide and olaparib plus abiraterone are FDA-approved for mCRPC treatment. While olaparib-abiraterone demonstrates superior economic viability in the U.S., this advantage comes at the expense of biomarker dependency and reduced generalizability to unselected patient cohorts. Conversely, although talazoparib plus enzalutamide lacks initial cost-effectiveness in both Chinese and U.S. healthcare systems prior to price adjustments, it exhibits robust clinical benefits across broad, unselected populations. With rational price reductions, the combination achieves cost-effectiveness within acceptable thresholds, positioning it as a promising first-line therapy for mCRPC. 5. Limitation This study has some limitations in evaluating the cost-effectiveness of talazoparib plus enzalutamide from U.S. and Chinese perspectives. First, the utility values lack localization for China. The Chinese model referenced utility values derived from the QQL questionnaire administered to the U.S. population[ 25 ], which introduces potential cultural bias due to differences in health preference weights between American and Chinese societies. Second, the analysis did not account for the economic impact of genetic mutations such as HRR alterations. The ASCO guidelines classify talazoparib plus enzalutamide as a Category 1A recommended treatment for patients with HRR pathway mutations. On the one hand, patients with HRR gene defects may have a higher economic value due to longer PFS survival after treatment with talazoparib plus enzalutamide. However, patient acceptance of genetic testing is still a worldwide problem, and it is estimated that only 37% of mCPRC patients have received genetic testing. On the other hand, the high cost of genetic testing may also make talazoparib plus enzalutamide less economical. Lastly, while China's WTP threshold was set at three times the national per capita GDP, regional economic disparities were not considered. In high-income cities like Shanghai, Hangzhou, and Shenzhen, elevated local payment capacities might render the talazoparib plus enzalutamide regimen cost-effective at subnational thresholds. 6. Conclusions Although the TALAPRO-2 study demonstrated statistically significant and clinically meaningful improvements in OS in patients with mCRPC with or without HRR gene mutations with the regimen of talazoparib plus enzalutamide versus placebo plus enzalutamide, due to the high cost of the drug talazoparib, the regimen of talazoparib plus enzalutamide did not show economy. To improve its economy, it is recommended to use the Big Panel genetic test covering HRR-related genes such as BRCA1/2, ATM, CDK12, etc., to screen the PARPi applicable population or refer to the conclusion of the OWSA to achieve a price reduction for talazoparib. For mCRPC patients not harboring HRR mutations, ARPI monotherapy (e.g., abiraterone plus prednisone) remains the standard first-line regimen, but some studies have suggested that combining with immunotherapy[ 26 , 27 ] or PI3K/AKT[ 28 , 29 ] pathway inhibitors may provide additional benefit. Abbreviations mCRPC: metastatic castration-resistant prostate cancer, ADT: Androgen deprivation therapy, AEs: adverse events, PARP: Poly (ADP-ribose) polymerase, PARPi: PARP inhibitor, PBO: placebo, AR: androgen receptor, QALYs: quality-adjusted life years, ICER: incremental cost-effectiveness ratio, WTP: Willingness-to-Pay; DDR: DNA damage repair, ASCO: American Society of Clinical Oncology, CSCO: Chinese Society of Clinical Oncology, IPD: individual patient data, OWSA: one-way sensitivity analysis, PSA: probabilistic sensitivity analysis Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and material Not applicable. Competing interests The authors declare that they have no competing interests. Funding This study was funded by the Key Medical Discipline of Hangzhou City (2021-21); the Key Medical Discipline of Zhejiang Province (2018–2–3); the Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province (2020E10021); the Zhejiang Province Medical and Health Science and Technology Program (2023KY933); and the Zhejiang Traditional Chinese Medicine Science and Technology Project (2023ZL565). Authors’ contributions JZ and ZL drafted the manuscript. JZ, ZL and QX finalized the paper and provided suggestions to improve it. YD and QX revised the paper and supervised this work. All the authors have read and approved the final manuscript. *These authors contributed equally to this work and should be considered co-first authors. References Siegel RL, Giaquinto AN, Jemal A: Cancer statistics, 2024 . 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Chen X, Wang M, Wang H, Yang J, Li X, Zhang R, Ding X, Hou H, Zhou J, Wu M: METTL3 inhibitor suppresses the progression of prostate cancer via IGFBP3/AKT pathway and synergizes with PARP inhibitor . Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2024, 179 :117366. Zhou S, Dai Z, Wang L, Gao X, Yang L, Wang Z, Wang Q, Liu Z: MET inhibition enhances PARP inhibitor efficacy in castration-resistant prostate cancer by suppressing the ATM/ATR and PI3K/AKT pathways . Journal of cellular and molecular medicine 2021, 25 (24):11157-11169. Zhang PF, Xie D, Li Q: Cost-effectiveness analysis of cabazitaxel for metastatic castration resistant prostate cancer after docetaxel and androgen-signaling-targeted inhibitor resistance . BMC cancer 2021, 21 (1):35. Mehrens D, Kramer KKM, Unterrainer LM, Beyer L, Bartenstein P, Froelich MF, Tollens F, Ricke J, Rübenthaler J, Schmidt-Hegemann NS et al : Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer . Journal of the National Comprehensive Cancer Network : JNCCN 2023, 21 (1):43-50.e42. Peters ML, de Meijer C, Wyndaele D, Noordzij W, Leliveld-Kors AM, van den Bosch J, van den Berg PH, Baka A, Gaultney JG: Dutch Economic Value of Radium-223 in Metastatic Castration-Resistant Prostate Cancer . Applied health economics and health policy 2018, 16 (1):133-143. Zeng X, Liu Q, Tan C, Wan X, Wang Y, Ma X: Alpha emitter radium-223 in patients with metastatic castration-resistant prostate cancer: A cost-utility analysis . Frontiers in pharmacology 2022, 13 :1003483. Li N, Zheng H, Huang Y, Zheng B, Cai H, Liu M: Cost-Effectiveness Analysis of Olaparib Maintenance Treatment for Germline BRCA-Mutated Metastatic Pancreatic Cancer . Frontiers in pharmacology 2021, 12 :632818. Zhang PF, Xie D, Li Q: Adding Enzalutamide to First-Line Treatment for Metastatic Hormone-Sensitive Prostate Cancer: A Cost-Effectiveness Analysis . Frontiers in public health 2021, 9 :608375. Lin Y, Li C, Wang C, Chen J, Huang Y: Atezolizumab plus bevacizumab and chemotherapy as first-line therapy for cervical cancer: a cost-effectiveness analysis in the US . Frontiers in immunology 2024, 15 :1481584. Hu X, Qu S, Yao X, Li C, Liu Y, Wang J: Abiraterone acetate and docetaxel with androgen deprivation therapy in high-volume metastatic hormone-sensitive prostate cancer in China: an indirect treatment comparison and cost analysis . Cost effectiveness and resource allocation : C/E 2019, 17 :27. Wu B, Zhang Q, Sun J: Cost-effectiveness of nivolumab plus ipilimumab as first-line therapy in advanced renal-cell carcinoma . Journal for immunotherapy of cancer 2018, 6 (1):124. Okumura H, Inoue S, Naidoo S, Holmstrom S, Akaza H: Cost-effectiveness analysis of enzalutamide for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer in Japan . Japanese journal of clinical oncology 2021, 51 (8):1319-1329. Additional Declarations No competing interests reported. Supplementary Files Additionalfiles.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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10:34:11","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":149662,"visible":true,"origin":"","legend":"\u003cp\u003eCost-effectiveness scatter plot in U.S. (A) and China (B).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6199993/v1/c1eee0da0c84375b4c1095bb.png"},{"id":78662520,"identity":"585d9784-ca88-4b65-9f1a-62ba277cb83a","added_by":"auto","created_at":"2025-03-17 10:26:11","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":100336,"visible":true,"origin":"","legend":"\u003cp\u003eCost-effectiveness acceptability curves for talazoparib under progressive price reductions in U.S. (A) and China 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Introduction","content":"\u003cp\u003eAccounting for nearly one-tenth of cancer mortality in American men, prostate cancer represents the second leading cause of male cancer incidence nationwide.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This mortality burden is primarily attributed to its high propensity for bone metastasis and the eventual failure of hormonal therapies. The proliferation of early-stage prostate cancer critically depends on androgen receptor (AR) signaling and its ligand testosterone, which has prompted the development of therapeutic strategies targeting both androgen biosynthesis and AR-mediated oncogenic pathways. Androgen deprivation therapy (ADT), encompassing surgical castration and pharmacologic approaches, aims to suppress systemic androgen synthesis. However, a subset of patients exhibit disease progression post-ADT through AR overexpression that sustains tumor growth in low-testosterone environments[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], leading to metastatic castration-resistant prostate cancer (mCRPC). To address this, second-generation AR competitive inhibitors including enzalutamide, apalutamide[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and androgen precursor synthesis inhibitors like abiraterone acetate have been employed in mCRPC management, demonstrating significant clinical benefits in multiple Phase III trials[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNearly one-third of individuals diagnosed with prostate cancer present with genetic alterations in DNA damage repair (DDR) pathways, predominantly involving homologous recombination repair (HRR)-associated genes. The HRR pathway encompasses multiple members including ATM, CHEK2, and BRCA1/2. An observational study demonstrated that patients with HRR mutations (HRRm) exhibited shorter overall survival and differential therapeutic responses to identical treatment modalities compared to non-HRRm counterparts[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Consequently, ctDNA genomic profiling to delineate molecular characteristics enables optimized therapeutic decision-making and prognostic evaluation[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Poly(ADP-ribose) polymerase (PARP), a critical enzyme in DNA damage repair, demonstrates enhanced activity mediated by AR inhibition during ADT, concomitant with downregulation of HRR gene expression. Given the high prevalence of homologous recombination repair deficiency in metastatic mCRPC, PARP inhibitors exert synthetic lethality by impairing DNA repair mechanisms, particularly when combined with ADT, thereby conferring survival benefits in advanced mCRPC. Recent phase III trials including PROfound and PROpel established that olaparib combined with abiraterone significantly prolongs progression free survival (PFS) and overall survival (OS) across all study populations, with enhanced clinical benefits observed in HRRm and BRCA1/2-mutated cohorts. This regimen has been endorsed as a Category 1A recommendation for mCRPC treatment in the 2024 American Society of Clinical Oncology (ASCO) guidelines. Subgroup analyses revealed striking efficacy differences: HRRm subgroups achieved rPFS HR\u0026thinsp;=\u0026thinsp;0.66 versus HR\u0026thinsp;=\u0026thinsp;0.89 in non-HRRm groups, with BRCA1/2-mutated cohorts demonstrating HR\u0026thinsp;=\u0026thinsp;0.29. These findings were corroborated in the PROfound cohort[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Olaparib and rucaparib have received US and Europe approval as first-line therapies for mCRPC patients with BRAC1/ 2mutations[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A majority of experts consensus strongly supports PARP inhibitor (PARPi) combination therapy with androgen receptor pathway inhibitors in BRCA1/2-altered patients, while demonstrating overwhelming opposition to PARP inhibitor use in DDR-intact mCRPC cases. Current treatment algorithms recommend referencing mHSPC therapeutic paradigms for DDR-wildtype mCRPC management[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn 2018, talazoparib received FDA approval for prostate cancer treatment and was subsequently designated as a first-line therapeutic agent for mCRPC by the Chinese Society of Clinical Oncology (CSCO) guidelines in 2020. The phase III TALAPRO-2 trial demonstrated that talazoparib plus enzalutamide significantly improved PFS and OS across the entire study population, achieving a 37% reduction in risk of disease progression or death (HR\u0026thinsp;=\u0026thinsp;0.62; 95% CI 0.475\u0026ndash;0.814).Subgroup analyses stratified by HRR gene mutation status revealed substantial therapeutic heterogeneity: the talazoparib plus enzalutamide cohort with HRRm exhibited median OS not reached after 52.5 months of follow-up, compared to 42.4 months in non-HRRm patients receiving the same combination. This underscores the critical impact of HRR mutational status on clinical outcomes with talazoparib based therapy. Notably, this study provides pivotal evidence that HRR mutation profiling constitutes a more robust predictor of therapeutic responsiveness to PARP inhibitor-ADT combination regimens than BRCA1/2 mutation status alone. (ASCO GU; February 13\u0026ndash;15, 2025).\u003c/p\u003e \u003cp\u003eAlthough the combination therapy of talazoparib and enzalutamide has demonstrated clinical efficacy in the TALAPRO-2 trial, its high cost compared to other PARP inhibitors[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] raises uncertainties regarding the cost-effectiveness of global implementation, particularly in middle-income countries where its potential to improve quality of life for mCRPC patients remains unverified. To optimize healthcare resource allocation, identify high-benefit patient subgroups, enhance scientific decision-making in treatment strategies and drug pricing, and balance multi-stakeholder interests, this study evaluates the cost-effectiveness of talazoparib plus enzalutamide versus enzalutamide monotherapy from the perspectives of U.S. and Chinese healthcare payers.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Population and intervention\u003c/h2\u003e \u003cp\u003eThis research strictly adhered to the updated Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022). Detailed compliance with each checklist item is provided in Additional file Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e. Based on the TALAPRO-2 clinical trial, the model simulated mCRPC patients aged 70 years (the median age of the clinical trial population) who had received continuous castration therapy (testosterone\u0026thinsp;\u0026le;\u0026thinsp;50 ng/dL) with ongoing ADT, presented radiologically confirmed bone or soft tissue metastases, and exhibited asymptomatic or mildly symptomatic disease. The target patient population was randomly assigned 1:1 to either the TALA arm or the placebo (PBO) group. The TALA arm received two 0.25 mg talazoparib capsules administered orally once daily plus four 40 mg enzalutamide capsules daily, while the PBO arm received two matching placebo capsules daily alongside four 40 mg enzalutamide capsules. Upon radiographically confirmed disease progression, second-line therapeutic regimens from the TALAPRO-2 supplementary appendix were initiated, with remaining progressive cases receiving best supportive care. Monitoring protocols followed the TALAPRO-2 study design during the initial 56 weeks of follow-up, transitioning thereafter to surveillance strategies recommended by the CSCO guidelines. Patients continued treatment until death, adverse event-induced discontinuation, or study endpoint attainment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Model construction\u003c/h2\u003e \u003cp\u003eThis study employed a dynamic Markov model constructed using TreeAge Pro 2022 software (TreeAge, Williamstown, MA) to evaluate the cost-effectiveness of talazoparib plus enzalutamide in treating mCRPC. Within the modeling framework, patients could transition between three mutually exclusive states: PFS, progressive disease (PD), and the absorbing state of death. As per model specifications, the initial health state for the entire cohort was defined as PFS and could transition between these states during disease progression. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) A 28-day cycle length was implemented to align with TALAPRO-2 treatment intervals, with a 30-year time horizon to sufficiently capture mortality events.\u003c/p\u003e \u003cp\u003eThe economic evaluation focused on three principal endpoints: total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). All cost and utility estimates underwent 3% and 5% annual discounting in US and China with half-cycle correction. Following the 2020 Chinese Pharmacoeconomic Evaluation Guidelines[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], willingness-to-pay (WTP) thresholds were set at \u003cspan\u003e$\u003c/span\u003e40,334 (3\u0026times;China\u0026prime;s 2024 per capita GDP) for China and \u003cspan\u003e$\u003c/span\u003e150,000 for the U.S.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Clinical data\u003c/h2\u003e \u003cp\u003eGiven the unavailability of original individual patient data (IPD), OS and PFS estimates for the mCRPC cohort were derived from Kaplan-Meier (KM) curves published in the TALAPRO-2 trial. For quantitative analysis of published survival data, the GetData Graph Digitizer platform (Version 2.26) was employed to capture data points from both OS and PFS curves published by TALAPRO-2 experiment, and R software (Version 4.3.2) was used to reconstruct IPD. Based on Guyot et al.\u0026rsquo;s[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] algorithm, Exponential, Weibull, Log-logistic, Log-normal, and Gompertz standard parametric survival functions were subsequently employed to fit and extrapolate survival curves. The final model selection was determined through a comprehensive evaluation incorporating Akakike Information Criterion (AIC) and Bayesian Information Criterion (BIC) statistical criteria, complemented by graphical assessment.(Additional file: Table S2 and Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e) The optimal distributions for OS and PFS survival curves were Log-logistic \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\text{S}\\left(\\text{t}\\right)=\\frac{1}{1+{\\left({\\lambda\\:}t\\right)}^{{\\gamma\\:}}}\\)\u003c/span\u003e\u003c/span\u003e and Log-normal \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:S\\left(t\\right)=1-{\\Phi\\:}\\left(\\frac{\\text{ln}t-{\\mu\\:}}{{\\sigma\\:}}\\right)\\)\u003c/span\u003e\u003c/span\u003e, fitting OS and PFS survival curves for talazoparib plus enzalutamide and placebo plus enzalutamide, respectively. Detailed fitting results can be found in the (Additional file: Table S3 and Figure S2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Transition probability\u003c/h2\u003e \u003cp\u003eThe disease progression dynamics in mCRPC patients were simulated using transition probability modeling, which incorporated the method of Latime et al.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] to calculate time-dependent transition probabilities between distinct health states within Markov models. (Additional file: Table S4) The transition probability from PFS to death was assumed to be the natural mortality. Based on OS and PFS survival functions, the specific-cycle transition probability between states was calculated using the following formula: \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\text{t}\\text{p}\\left({\\mu\\:}\\right)=1-\\frac{\\text{S}\\left(\\text{t}\\right)}{\\text{S}\\left(\\text{t}-{\\mu\\:}\\right)}\\)\u003c/span\u003e\u003c/span\u003e where \u0026micro; is the cycle length.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Cost and utility\u003c/h2\u003e \u003cp\u003eThis study adopts the perspectives of third-party payers in China and the U.S., considering only direct medical costs, which include first-line treatment drug costs, second-line treatment costs after disease progression, examination costs, follow-up costs, hospice care costs, and the treatment costs of the top five severe adverse events (AEs) (grade\u0026thinsp;\u0026ge;\u0026thinsp;3). (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) The price adjustments were made using the consumer price index (CPI) to reflect inflation, and all costs were adjusted to the 2025 US dollars according to the formula from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.infationtool.com\u003c/span\u003e\u003cspan address=\"https://www.infationtool.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Since second-line treatments such as Cabazitaxel and Doxitaxel require dosing based on patient body surface area, we assume the average weight of US and Chinese patients to be 70 kg and 65 kg, respectively, to calculate dosing and costs, which are then incorporated into sensitivity analysis. As Lutetium is not yet available in China, its cost in China is estimated by multiplying the US cost by the ratio of talazoparib costs in China and the US. Other costs are obtained from local tertiary hospital fee standards, published literature, and relevant websites, and all second-line treatment costs are weighted before being input into the model. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical outcomes for each cohort\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTalazoparib plus enzalutamide\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePlacebo plus enzalutamide\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRisk of grade3\u0026thinsp;~\u0026thinsp;5 AEs (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal AEs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e75.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProportion receiving second-line treatment (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDocetaxel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCabazitaxel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbiraterone plus prednisone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOlaparib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLutetium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBSC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eAEs: Adverse events, BSC: Best supportive care\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCost in US and China\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eInput Parameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSA range\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDistribution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSA range\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eDistribution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrice of drug\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrice of talazoparib per 0.25 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e510.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e408.39\u0026thinsp;~\u0026thinsp;612.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eyaozh.com\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e71.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e57.34\u0026thinsp;~\u0026thinsp;86.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003ehospital charge\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrice of talazoparib per cycle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28587.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22869.73\u0026thinsp;~\u0026thinsp;34304.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eyaozh.com\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e4014.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3211.26\u0026thinsp;~\u0026thinsp;4816.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003ehospital charge\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrice of enzalutamide per 40 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e125.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100.06\u0026thinsp;~\u0026thinsp;150.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e6.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.28\u0026thinsp;~\u0026thinsp;7.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eyaozh.com\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrice of enzalutamide per cycle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15072.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12057.81\u0026thinsp;~\u0026thinsp;18086.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e739.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e591.36\u0026thinsp;~\u0026thinsp;887.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eyaozh.com\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCost of second-line treatment per cycle\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDocetaxel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2228.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1783.16\u0026thinsp;~\u0026thinsp;2674.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e961.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e769.17\u0026thinsp;~\u0026thinsp;1153.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCabazitaxel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11989.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9591.58\u0026thinsp;~\u0026thinsp;14387.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e1642.3592\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1313.89\u0026thinsp;~\u0026thinsp;1970.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eselleck.cn\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbiraterone plus prednisone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12457.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9966.10\u0026thinsp;~\u0026thinsp;14949.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e638.9923\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e511.19\u0026thinsp;~\u0026thinsp;766.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOlaparib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16022.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12818.27\u0026thinsp;~\u0026thinsp;19227.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e1820.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1456.54\u0026thinsp;~\u0026thinsp;2184.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLutetium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30628.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24502.63\u0026thinsp;~\u0026thinsp;36753.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e4594.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3675.39\u0026thinsp;~\u0026thinsp;5513.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13906.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11124.96\u0026thinsp;~\u0026thinsp;16687.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e20,488.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e16390.89\u0026thinsp;~\u0026thinsp;24586.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCost of monitoring per unit\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.75\u0026thinsp;~\u0026thinsp;32.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e7.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6.05\u0026thinsp;~\u0026thinsp;9.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e972.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e778.10\u0026thinsp;~\u0026thinsp;1167.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e230.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e184.08\u0026thinsp;~\u0026thinsp;276.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone scanning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e275.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e220.53\u0026thinsp;~\u0026thinsp;330.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e153.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e122.68\u0026thinsp;~\u0026thinsp;184.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory examination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.13\u0026thinsp;~\u0026thinsp;99.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e33.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e26.69\u0026thinsp;~\u0026thinsp;40.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCirculating tumour cell enumeration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e937.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e749.60\u0026thinsp;~\u0026thinsp;1124.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eFairhealthconsumer.org\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e431.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e344.80\u0026thinsp;~\u0026thinsp;517.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRED BOOK\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCost of BSC per cycle\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1319.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1055.42\u0026thinsp;~\u0026thinsp;1583.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e77.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e62.04\u0026thinsp;~\u0026thinsp;93.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCost of terminal care\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100908.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80726.50\u0026thinsp;~\u0026thinsp;121089.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e2288.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1830.59\u0026thinsp;~\u0026thinsp;2745.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCost of follow up of per unit\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e458.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e367.18\u0026thinsp;~\u0026thinsp;550.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e56.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e44.81\u0026thinsp;~\u0026thinsp;67.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCost of managing AEs (grade\u0026thinsp;\u0026gt;\u0026thinsp;3) per event\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1233.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e986.69\u0026thinsp;~\u0026thinsp;1480.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e579.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e463.76\u0026thinsp;~\u0026thinsp;695.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29643.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23714.58\u0026thinsp;~\u0026thinsp;35571.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e63.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e51.20\u0026thinsp;~\u0026thinsp;76.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2487.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1990.11\u0026thinsp;~\u0026thinsp;2985.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e598.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e479.08\u0026thinsp;~\u0026thinsp;718.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2637.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2109.97\u0026thinsp;~\u0026thinsp;3164.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e16.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e13.45\u0026thinsp;~\u0026thinsp;20.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10721.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8577.42\u0026thinsp;~\u0026thinsp;12866.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e88.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e70.91\u0026thinsp;~\u0026thinsp;106.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiscount rate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026thinsp;~\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u0026thinsp;~\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBody surface\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.74\u0026thinsp;~\u0026thinsp;2.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e1.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.38\u0026thinsp;~\u0026thinsp;2.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGamma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003eSA: Sensitivity analysis PSA: Prostate specific antigen, CT: Computed tomography, AE: Adverse event, BSC: Best supportive care, *Since Lutetium is not approved in China, its cost in the Chinese context was estimated based on the US market price, with the cost conversion ratio referenced to the price differential of Talazoparib between China and the United States\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eUtility values, ranging between 0 and 1, measure patients' quality of life and indirectly reflect the benefits of medical interventions. The utility values for PFS and PD states are obtained from relevant literature, while the utility decrements due to AEs include only the disutility values of the top five AEs with grade\u0026thinsp;\u0026ge;\u0026thinsp;3 severity. (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUtility and disutility in model\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHealth utility\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSA range\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDistribution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgressive disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.52\u0026thinsp;~\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgression-free survival\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.61\u0026thinsp;~\u0026thinsp;0.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDisutility\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.09\u0026thinsp;~\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.08\u0026thinsp;~\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.38\u0026thinsp;~\u0026thinsp;0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Sensitivity analysis\u003c/h2\u003e \u003cp\u003eWe used one-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) to explore the impact of each variable input into the model on the ICER. In the OWSA, the low and high values of each variable were determined by \u0026plusmn;\u0026thinsp;20% of the baseline value, with the high value of the discount rate set at 0.8 and the low value at 0. The results of the OWSA were presented using Tornado diagram. Additionally, we conducted 10,000 Monte Carlo simulations for the PSA, assuming that the costs in the model followed a Gamma distribution, while utility values, AE rates, and the proportion of second-line treatment choices were assumed to follow a Beta distribution. The results of the PSA were presented in the form of cost-effectiveness acceptability curves and ICER scatterplots.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7 Scenario analysis\u003c/h2\u003e \u003cp\u003eTo further explore the cost-effectiveness of talazoparib plus enzalutamide in the treatment of mCRPC, we conducted a price reduction simulation for talazoparib, assuming price reductions of 20%, 40%, 60%, and 80%, respectively. The analysis compared changes in the ICER and the probability of cost-effectiveness acceptability.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Result","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Base-case analysis\u003c/h2\u003e \u003cp\u003eThe results of the cost-effectiveness analysis showed that in the Chinese perspective, the total cost of treatment with talazoparib in combination with enzalutamide for mCRPC patients was \u003cspan\u003e$\u003c/span\u003e97,286, which amounted to an incremental cost of \u003cspan\u003e$\u003c/span\u003e53,537 compared to the total cost of \u003cspan\u003e$\u003c/span\u003e43,748 for treatment with enzalutamide. Compared to the enzalutamide-treated group that averaged or gained 2.25 QALYs, the talazoparib in combination with enzalutamide group could gain an additional 0.93 QALYs with an ICER of \u003cspan\u003e$\u003c/span\u003e57,635.76/QALY, which was greater than the Chinese payer WTP, suggesting that talazoparib in combination with enzalutamide was not economical. In the U.S. perspective, the incremental cost of the talazoparib plus enzalutamide group was \u003cspan\u003e$\u003c/span\u003e708,234, and its incremental utility and ICER were 1.1 QALYs and \u003cspan\u003e$\u003c/span\u003e646,743.72/QALY, respectively. From the Chinese perspective, the total cost of talazoparib plus enzalutamide was \u003cspan\u003e$\u003c/span\u003e97,286, which was \u003cspan\u003e$\u003c/span\u003e53,537 higher than enzalutamide monotherapy. Its ICER of \u003cspan\u003e$\u003c/span\u003e57,635.76/QALY was much higher than the Chinese payer threshold (\u003cspan\u003e$\u003c/span\u003e40,334/QALY), suggesting that this combination regimen is not cost-effective in China. (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResult of base-case analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStrategy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eUS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c12\" namest=\"c8\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal cost (\u003cspan\u003e$\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIC (\u003cspan\u003e$\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQALYs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eICER (\u003cspan\u003e$\u003c/span\u003e/QALY)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTotal costs (\u003cspan\u003e$\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eIC (\u003cspan\u003e$\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eQALYs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eIE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eICER (\u003cspan\u003e$\u003c/span\u003e/QALY)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePBO\u0026thinsp;+\u0026thinsp;ENZA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e532634.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e43748.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTALA\u0026thinsp;+\u0026thinsp;ENZA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1240867.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e708233.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e646743.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e97285.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e53536.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e57635.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eIC: Incremental Cost, IE: Incremental Effectiveness, ICER: Incremental Cost-Effectiveness Ratio, QALYs: Quality-Adjusted Life Years, PBO: Placebo, TALA: Talazoparib, ENZA: Enzalutamide\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Sensitivity analysis\u003c/h2\u003e \u003cp\u003eOWSA showed that the most influential parameter on ICER in both the US and Chinese perspectives was the utility of PFS state. Of the remaining parameters entered into the model, those that had a greater impact on the ICER values were the unit price of talazoparib, the unit price of enzalutamide, and the utility of PD state, respectively. Changes in other variables had less impact on the stability of the model, showing that the model is stable and the conclusions of this study are reliable, all parameters of in the range of changes cannot make the ICER value lower than the WTP. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) PSA of the scatterplot shows that all scatters fall above the WTP line, (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) that is, none of the treatment of razoparib in combination with enzalutamide is economical compared with enzalutamide alone, the Chinese threshold value of \u003cspan\u003e$\u003c/span\u003e40,334 when accepting the proportion of 1.33%, and 0% acceptance at a WTP of \u003cspan\u003e$\u003c/span\u003e150,000 in the U.S.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Scenario analysis\u003c/h2\u003e \u003cp\u003eAfter doing 20%, 40%, 60%, and 80% price reductions for talazoparib 0.25 mg unit price, it was found that the talazoparib plus enzalutamide group demonstrated economy with an acceptable probability of 64.87% for the Chinese payer perspective with a price reduction ratio of 40%. For the U.S. payer perspective, on the other hand, even with a price reduction percentage of 80%, talazoparib still did not demonstrate economy, resulting in talazoparib not demonstrating economy. Further study found that in the Chinese payer perspective, the talazoparib plus enzalutamide group showed higher economy when the price reduction percentage reached 34.5%. (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResult of scenario analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eReduction rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdjusted ICER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReduction ratio of ICER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAcceptability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAdjusted ICER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eReduction ratio of ICER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAcceptability\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e577605.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.69%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47208.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18.09%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18.64%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e508466.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.38%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36781.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e36.18%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e69.43%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e439328.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.07%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26353.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e54.28%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e97.28%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e80%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e370189.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.76%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15926.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e72.37%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e99.96%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eICER: Incremental cost-effectiveness ratio\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eProstate cancer is a malignancy with persistently high incidence in males. Following ADT treatment, patients may transition from hormone-sensitive to castration-resistant status, indicating tumor androgen independence and failure of castration therapy. The HRR gene-deficient cells experience a functional impairment in their DNA double-strand break repair mechanisms. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Since the proposal of the concept that PARPi induce synthetic lethality in HRR-deficient tumor cells by blocking the backup DNA repair pathway[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] first-generation PARP inhibitors such as olaparib and talazoparib have been developed and entered clinical trials. The TALAPRO-2 trial investigated the clinical significance of talazoparib plus enzalutamide in mCRPC populations. Results showed that talazoparib extended patient OS by 14 months and PFS by 18.4 months. In January 2024, the European Commission granted regulatory approval for the talazoparib-enzalutamide combination therapy in the management of mCRPC without clinical indications for chemotherapy, marking the first PARPi regimen certified by the European Commission. A network meta-analysis indicated that, compared with other PARPi combined with AR signaling inhibitor therapies, talazoparib plus enzalutamide holds the greatest potential to prolong PFS, thereby reducing the need for second-line treatments [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, the high cost of talazoparib limits its economic viability and clinical application. This investigation represents, to our knowledge, the inaugural economic evaluation of talazoparib-enzalutamide combination therapy as a first-line treatment for mCRPC, incorporating both Chinese and U.S. healthcare perspectives. From the Chinese and U.S. perspectives, the cost of talazoparib plus enzalutamide significantly exceeded that of enzalutamide monotherapy, with incremental costs per additional QALYs gained reaching \u003cspan\u003e$\u003c/span\u003e57,635.76 and \u003cspan\u003e$\u003c/span\u003e646,743.72 respectively, both surpassing our pre-defined WTP thresholds. Consequently, the combination therapy lacks economic feasibility in both countries. Univariate sensitivity analysis revealed that key drivers of ICER in both contexts were utility values during PFS, drug prices of talazoparib and enzalutamide, utility values during PD, and discount rates. This highlights the critical impact of scientific drug pricing on the acceptability of this regimen.\u003c/p\u003e \u003cp\u003eThe pronounced influence of PFS utility values on ICER suggests that selecting patients with HRR gene mutations for talazoparib plus enzalutamide therapy could extend PFS duration, thereby increasing QALYs and reducing ICER. This supports the necessity of HRR gene testing at diagnosis. Price reduction simulations for talazoparib demonstrated that a 20% price cut in China reduced ICER to \u003cspan\u003e$\u003c/span\u003e47,208.45, increasing cost-effectiveness acceptability probability from \u0026lt;\u0026thinsp;1\u0026ndash;15%, indicating that moderate price adjustments could substantially improve economic viability\u0026mdash;a finding particularly relevant given talazoparib\u0026rsquo;s high pricing in China.\u003c/p\u003e \u003cp\u003eAt 40% price reduction, the combination therapy demonstrated superior cost-effectiveness versus enzalutamide monotherapy. Further analysis showed that a 34.5% price reduction achieved 50% cost-effectiveness probability. In China, drug pricing is closely tied to national medical insurance inclusion, and future centralized procurement/price negotiations could reasonably bring ICER within acceptable ranges. In the U.S. perspective, we found that even with an 80% price reduction for talazoparib, the benefit of gaining one additional QALYs when the WTP is \u003cspan\u003e$\u003c/span\u003e150,000 still does not cover the incremental cost of \u003cspan\u003e$\u003c/span\u003e370,189.78. And for every 20% price reduction of talazoparib, the ICER value was only reduced by 10.69%, suggesting that the high cost of other adverse effect management and second-line treatment is also one of the reasons why talazoparib in combination with enzalutamide does not show economy. On the one hand, the U.S. has a high degree of drug marketization, and the price of PARPi drugs such as talazoparib fluctuates with patent expiration and extensive development of PARP inhibitors; On the other hand, PARP inhibitors have shown clinical benefits in malignant tumors such as breast cancer [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] the expansion of market capacity may lead to increased competition in the market, further driving the price of talazoparib back down. Currently, the higher price of talazoparib is not reflective of its true value to U.S. payers, and we expect that talazoparib will achieve efficacy-based pricing to reduce payer risk. The sensitivity of the model to talazoparib demonstrates that there are price distortions in the current price of talazoparib, likely due to patent protection and market monopoly, and that reasonable price reductions and differentiated pricing based on regional levels of development could correct the price distortions and improve the economics of talazoparib in combination with enzalutamide.\u003c/p\u003e \u003cp\u003eData from the TALAPRO-2 trial showed that the combination therapy reduced the risk of progression of the disease by 37% but the price would need to be commensurate with the health benefit in order to maximize its health-promoting effect. Fortunately, Pfizer runs a patient assistance program that makes lower-cost treatment with talazoparib available to some low- and middle-income populations. The PROpel trial, conducted concurrently with TALAPRO-2, explored the clinical efficacy of olaparib in combination with abiraterone in patients with mCRPC. Olaparib as approved by the FDA as a treatment for mCRPC patients with BRAC mutations [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], shows very different results in the study of Xu et al[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. They found that olaparib in combination with abiraterone was also not economical in China, which is consistent with our opinion, whereas in the US perspective, the cost of the olaparib plus abiraterone treatment group was instead decreased by \u003cspan\u003e$\u003c/span\u003e69,675.20 compared to the control group and higher utility values were obtained (incremental effectiveness\u0026thinsp;=\u0026thinsp;0.23), which is undoubtedly economical in the US perspective. There are several reasons for this difference.1) Olaparib costs \u003cspan\u003e$\u003c/span\u003e17,313.88 for a treatment cycle in the U.S. market after discounting to 2025 dollars, which is only 60% of the cost of talazoparib over a treatment cycle, making it more economical;2)Xu et al.'s data were derived from the PROfound cohort[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], which exclusively enrolled mCRPC patients with BRCA1/2 or ATM defects. In contrast, the TALAPRO-2 cohort included an all-comer population regardless of HRR gene mutation status. Our study simulated the cost-effectiveness of talazoparib plus enzalutamide in this unselected population, where the incremental benefits were understandably lower than in populations with PARP inhibitor-targetable genetic alterations. This indirectly indicates that while olaparib demonstrates better economic viability in the U.S., its target population is narrower than talazoparib's. The cost-effectiveness of olaparib in genetically unselected broad populations remains uncertain. 3) The PROfound trial reported substantially fewerAEs than the TALAPRO-2 trial. In the olaparib-abiraterone treatment arm, the incidence of grade\u0026thinsp;\u0026ge;\u0026thinsp;3 overall AEs and grade\u0026thinsp;\u0026ge;\u0026thinsp;3 anemia was 51% and 21% respectively, compared to 75% and 46% in the talazoparib plus enzalutamide arm. Combined with the 19-fold higher cost of AEs management per treatment cycle in the U.S. versus China, these factors led to lower total costs for olaparib plus abiraterone therapy. Consequently, its ICER against the comparator was more favorable, thereby demonstrating economic viability. Srinivas et al[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] conducted a cost-effectiveness analysis of olaparib combined with abiraterone for BRCA1/2-mutated mCRPC patients from an Australian perspective. The results showed an incremental cost of \u003cspan\u003e$\u003c/span\u003e4884.141 for an additional 0.06QLAYs yielding an ICERof \u003cspan\u003e$\u003c/span\u003e91138/QALY, At Australia's defined WTP threshold of \u003cspan\u003e$\u003c/span\u003e62,289.772, this regimen was not cost-effective. Price reduction analysis revealed that a 30% reduction in olaparib's monotherapy price was required to achieve\u0026thinsp;\u0026gt;\u0026thinsp;50% probability of cost-effectiveness acceptability for the olaparib plus enzalutamide. In conclusion, both talazoparib plus enzalutamide and olaparib plus abiraterone are FDA-approved for mCRPC treatment. While olaparib-abiraterone demonstrates superior economic viability in the U.S., this advantage comes at the expense of biomarker dependency and reduced generalizability to unselected patient cohorts. Conversely, although talazoparib plus enzalutamide lacks initial cost-effectiveness in both Chinese and U.S. healthcare systems prior to price adjustments, it exhibits robust clinical benefits across broad, unselected populations. With rational price reductions, the combination achieves cost-effectiveness within acceptable thresholds, positioning it as a promising first-line therapy for mCRPC.\u003c/p\u003e"},{"header":"5. Limitation","content":"\u003cp\u003eThis study has some limitations in evaluating the cost-effectiveness of talazoparib plus enzalutamide from U.S. and Chinese perspectives. First, the utility values lack localization for China. The Chinese model referenced utility values derived from the QQL questionnaire administered to the U.S. population[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], which introduces potential cultural bias due to differences in health preference weights between American and Chinese societies. Second, the analysis did not account for the economic impact of genetic mutations such as HRR alterations. The ASCO guidelines classify talazoparib plus enzalutamide as a Category 1A recommended treatment for patients with HRR pathway mutations. On the one hand, patients with HRR gene defects may have a higher economic value due to longer PFS survival after treatment with talazoparib plus enzalutamide. However, patient acceptance of genetic testing is still a worldwide problem, and it is estimated that only 37% of mCPRC patients have received genetic testing. On the other hand, the high cost of genetic testing may also make talazoparib plus enzalutamide less economical. Lastly, while China's WTP threshold was set at three times the national per capita GDP, regional economic disparities were not considered. In high-income cities like Shanghai, Hangzhou, and Shenzhen, elevated local payment capacities might render the talazoparib plus enzalutamide regimen cost-effective at subnational thresholds.\u003c/p\u003e"},{"header":"6. Conclusions","content":"\u003cp\u003eAlthough the TALAPRO-2 study demonstrated statistically significant and clinically meaningful improvements in OS in patients with mCRPC with or without HRR gene mutations with the regimen of talazoparib plus enzalutamide versus placebo plus enzalutamide, due to the high cost of the drug talazoparib, the regimen of talazoparib plus enzalutamide did not show economy. To improve its economy, it is recommended to use the Big Panel genetic test covering HRR-related genes such as BRCA1/2, ATM, CDK12, etc., to screen the PARPi applicable population or refer to the conclusion of the OWSA to achieve a price reduction for talazoparib. For mCRPC patients not harboring HRR mutations, ARPI monotherapy (e.g., abiraterone plus prednisone) remains the standard first-line regimen, but some studies have suggested that combining with immunotherapy[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] or PI3K/AKT[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] pathway inhibitors may provide additional benefit.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003emCRPC: metastatic castration-resistant prostate cancer, ADT: Androgen deprivation therapy, AEs: adverse events, PARP: Poly (ADP-ribose) polymerase, PARPi: PARP inhibitor, PBO: placebo, AR: androgen receptor, QALYs: quality-adjusted life years, ICER: incremental cost-effectiveness ratio, WTP: Willingness-to-Pay; DDR: DNA damage repair, ASCO: American Society of Clinical Oncology, CSCO: Chinese Society of Clinical Oncology, IPD: individual patient data, OWSA: one-way sensitivity analysis, PSA: probabilistic sensitivity analysis\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and material\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Key Medical Discipline of Hangzhou City (2021-21); the Key Medical Discipline of Zhejiang Province (2018–2–3); the Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province (2020E10021); the Zhejiang Province Medical and Health Science and Technology Program (2023KY933); and the Zhejiang Traditional Chinese Medicine Science and Technology Project (2023ZL565).\u003c/p\u003e\n\u003cp\u003eAuthors’ contributions\u003c/p\u003e\n\u003cp\u003eJZ and ZL drafted the manuscript. JZ, ZL and QX finalized the paper and provided suggestions to improve it. YD and QX revised the paper and supervised this work. All the authors have read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e*These authors contributed equally to this work and should be considered co-first authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSiegel RL, Giaquinto AN, Jemal A: \u003cstrong\u003eCancer statistics, 2024\u003c/strong\u003e. \u003cem\u003eCA: a cancer journal for clinicians \u003c/em\u003e2024, \u003cstrong\u003e74\u003c/strong\u003e(1):12-49.\u003c/li\u003e\n\u003cli\u003eDai C, Dehm SM, Sharifi N: \u003cstrong\u003eTargeting the Androgen Signaling Axis in Prostate Cancer\u003c/strong\u003e. \u003cem\u003eJournal of clinical oncology : official journal of the American Society of Clinical Oncology \u003c/em\u003e2023, \u003cstrong\u003e41\u003c/strong\u003e(26):4267-4278.\u003c/li\u003e\n\u003cli\u003eChen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG, Sawyers CL: \u003cstrong\u003eMolecular determinants of resistance to 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\u003cstrong\u003e51\u003c/strong\u003e(8):1319-1329.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"metastatic castration-resistant prostate cancer, Markov model, talazoparib, enzalutamide, cost-effectiveness","lastPublishedDoi":"10.21203/rs.3.rs-6199993/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6199993/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe TALAPRO-2 trial demonstrated that the combination of talazoparib and enzalutamide significantly improved both progression-free survival (PFS) and overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, the cost-effectiveness of this regimen remains unclear due to its high cost. This study aims to evaluate the cost-effectiveness of this combination compared to enzalutamide monotherapy as a first-line treatment for mCRPC.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eBased on data from the TALAPRO-2 trial, a dynamic Markov model was constructed to simulate disease progression in mCRPC patients. From the perspectives of US and Chinese payers, total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER) were considered as the primary outputs in the model. One-way sensitivity analysis and probabilistic sensitivity analysis were used to validate the robustness of the model. Price reduction analysis provides an evidence-based basis for drug pricing and health insurance negotiations by quantifying the impact of price adjustments on economics.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn the baseline analysis, the ICERs for talazoparib plus enzalutamide were \u003cspan\u003e$\u003c/span\u003e646,743.72/QALY and \u003cspan\u003e$\u003c/span\u003e57,635.76/QALY from the U.S. and China perspectives, respectively, which were above the willingness-to-pay thresholds (\u003cspan\u003e$\u003c/span\u003e150,000 in the U.S. and \u003cspan\u003e$\u003c/span\u003e40,334 in China). Sensitivity analyses showed that PFS utility values and drug prices impacted the results most. Price adjustment scenarios showed that China needed a 34.5% price reduction to achieve affordability, whereas the U.S. remained unaffordable even with an 80% price reduction.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eAt current pricing, talazoparib plus enzalutamide is not cost-effective for mCRPC patients. Optimizing its economic viability may be possible through genetic testing to screen for HRR mutation-positive populations or price negotiations to reduce drug costs. The study supports differentiated pricing strategies to balance clinical benefits with the rational allocation of healthcare resources.\u003c/p\u003e","manuscriptTitle":"Cost-effectiveness of talazoparib plus enzalutamide as first-line therapy in metastatic castration-resistant prostate cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-17 10:18:06","doi":"10.21203/rs.3.rs-6199993/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"15229bf4-a9d2-47d1-ac8a-7638980fb437","owner":[],"postedDate":"March 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-17T10:24:02+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-17 10:18:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6199993","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6199993","identity":"rs-6199993","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}