Comparative cost-effectiveness of tislelizumab plus chemotherapy versus standard chemotherapy in first-line treatment for extensive-stage small cell lung cancer: perspectives from the U.S. and Chinese healthcare systems

Comparative cost-effectiveness of tislelizumab plus chemotherapy versus standard chemotherapy in first-line treatment for extensive-stage small cell lung cancer: perspectives from the U.S. and Chinese healthcare systems | 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 Comparative cost-effectiveness of tislelizumab plus chemotherapy versus standard chemotherapy in first-line treatment for extensive-stage small cell lung cancer: perspectives from the U.S. and Chinese healthcare systems Wenwang Lang, Qi Ai, Yulong He, Yufei Pan, Qinling Jiang, Ming Ouyang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4451605/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Sep, 2024 Read the published version in International Journal of Clinical Pharmacy → Version 1 posted 6 You are reading this latest preprint version Abstract Background Tislelizumab combined with chemotherapy has shown significant clinical benefits in improving overall survival compared to chemotherapy alone for patients with extensive-stage small-cell lung cancer (ES-SCLC). Aim This study aimed to evaluate its cost-effectiveness for both US and Chinese ES-SCLC patient populations. Method We conducted an economic evaluation using a Markov state-transition model, reflecting the perspectives of US and Chinese healthcare payers. Baseline patient characteristics and essential clinical data were obtained from the RATIONALE-312 trial. The costs and utilities were derived from open-access databases and published literature. The primary outcomes measured included quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Uncertainties in the model were addressed by probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWSA). Results In the base-case analysis, the addition of tislelizumab to chemotherapy provided an incremental gain of 0.27 QALYs at an additional cost of $ 8,352.18, resulting in an ICER of $ 31,136.52 per QALY. Although below the willingness-to-pay (WTP) threshold of China of $ 38,042.49 per QALY, the cost-effectiveness was marginal, with an INHB of 0.05 QALYs and an INMB of $ 1,852.49. In the US, despite a slightly higher effectiveness gain of 0.29 QALYs, the increased cost of $ 45,157.35 resulted in an unfavorable ICER of $ 157,117.67 per QALY, exceeding the US WTP threshold of $ 150,000.00. PSA showed probabilities of cost-effectiveness of tislelizumab plus chemotherapy at 92.52% in China and 44.07% in the US. Conclusions Tislelizumab with chemotherapy may be a cost-effective first-line treatment option for ES-SCLC in China but not the US, highlighting significant geographical disparities in healthcare economics. Cost-effectiveness extensive-stage small-cell lung cancer tislelizumab chemotherapy Markov mode Figures Figure 1 Figure 2 Figure 3 Figure 4 Impact statements This study is the first to evaluate the cost-effectiveness of tislelizumab plus chemotherapy as first-line therapy for ES-SCLC from both the US and China perspectives. Tislelizumab with chemotherapy may be a cost-effective first-line treatment option for ES-SCLC in China, but not meet the same cost-effectiveness criteria in the US healthcare system. Introduction Lung cancer remains the leading cause of cancer-related mortality worldwide and is the second most common cancer diagnosed [1–3]. Small cell lung cancer (SCLC) accounts for about 15% of all lung cancer cases and is marked by its highly aggressive nature and the tendency to early metastasis. Most SCLC patients (80–85%) are identified with extensive-stage disease (ES-SCLC), which is associated with a poor prognosis. For decades, platinum-based chemotherapy combinations have been the cornerstone of first-line treatment for ES-SCLC, but survival rates remain inadequate [4, 5]. Despite initial sensitivity to chemotherapy, almost all patients with ES-SCLC relapse within 6 months, leading to a bleak 5-year survival rate of less than 5% [6, 7]. Although initial progress was slow, the introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the therapeutic landscape for ES-SCLC. Three phase III trials incorporating atezolizumab, durvalumab, or adebrelimab with chemotherapy have shown significant improvements in overall survival (OS) benefits [8–11]. A global randomized phase III trial (ASTRUM-005) demonstrated that the combination of the anti-PD-1 antibody serplulimab with chemotherapy substantially extended progression-free survival (PFS) and OS [12]. Tislelizumab, a PD-L1/PD-L2 signaling antagonist, has demonstrated the potential to increase cytokine production and reactivate T cell function, contributing to immune-mediated tumor cell destruction[13]. In the RATIONALE-312 study [14], tislelizumab combined with chemotherapy produced a statistically significant OS advantage over placebo combined with chemotherapy (stratified hazard ratio [HR] = 0.75 [95% confidence ratio (CI): 0.61–0.93]; one-sided p = 0.0040; median: 15.5 [95% CI: 13.5–17.1] months versus 13.5 months [95% CI: 12.1–14.9], respectively). Additionally, PFS significantly favored the tislelizumab group (stratified HR = 0.64 [95% CI: 0.52–0.78]; p < 0.0001; median: 4.7 [95% CI: 4.3–5.5] months versus 4.3 months [95% CI: 4.2–4.4], respectively). Grade ≥ 3 treatment-related adverse events, mainly hematologic, occurred in 86% of the participants in both treatment arms. The advent of tislelizumab may potentially shape the treatment markets for ES-SCLC in both the US and China with first-line ICIs. Tislelizumab is expected to be the first anti-PD-1 antibody approved globally. Despite these promising clinical outcomes, the financial implications of this combination therapy, which is more expensive than chemotherapy alone, cannot be overlooked. The cost of tislelizumab in China is approximately $ 400 per cycle (21 days), compared to $ 60 for the standard chemotherapy regimen, suggesting a possible need for price adjustments. Meanwhile, the price of tislelizumab in the US remains undisclosed. This study aimed to evaluate the cost-effectiveness of tislelizumab combined with chemotherapy versus chemotherapy alone as first-line treatment for previously untreated ES-SCLC patients from the perspective of US and Chinese healthcare payers to guide drug pricing strategies. Materials and Methods Patients and intervention This study was conducted according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist [15]. Participants were required to be 18 years or older and have histologically or cytologically ES-SCLC, determined by expert pathologists and defined by the Seventh Edition of the American Joint Committee on Cancer (AJCC) as Stage IV (T any, N any, M1a or M1b), or T3-4 due to multiple lung nodules that were too widespread, or with a tumor or nodal volume too large to be included in a tolerable irradiation plan. Patients had to have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1, a life expectancy ≥ 12 weeks, adequate organ function, and no previous systemic treatment for ES-SCLC. The induction phase included four 21-day cycles of intravenous tislelizumab 200 mg or placebo administered every three weeks (Q3W), combined with etoposide (100 mg/m² intravenously on days 1–3 of each cycle) and carboplatin (area under the plasma or serum concentration-time curve = 5) on the first day of each cycle. After the induction phase, maintenance therapy with 200 mg intravenous tislelizumab or placebo Q3W continued until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent. Tumor imaging, including Positron Emission Tomography-Computed Tomography (PET-CT) scan, every 6 weeks (± 7 days) for the first 48 weeks following the first day of treatment, and every 9 weeks (± 7 days) after that. A total of 306 patients (67%) received additional systemic anticancer treatments after discontinuing the study medications: 136 patients (60%) from the tislelizumab group and 170 patients (74%) from the placebo group. The most prevalent treatments in both groups were conventional chemotherapies, utilized by 124 patients (55%) in the tislelizumab group and 155 patients (67%) in the placebo group. The selection of chemotherapies, not fully specified, followed recommendations from the National Comprehensive Cancer Network (NCCN)[16], the Chinese Society of Clinical Oncology (CSCO) guidelines, findings from the RATIONALE-312 trial, and general clinical practice. Subsequent therapies included combinations such as topotecan with cisplatin or simply the best supportive care. The body surface area and creatinine clearance rates were assumed to be similar to those reported in previous studies [17]. The cost implications of adverse events (AEs) were assessed using data from the RATIONALE-312 trial. Our analysis focused exclusively on serious adverse events (SAEs) of grade 3 or 4 with an incidence rate greater than 3%. These SAEs included anemia, reduced platelet count, and decreased neutrophil count. The cost associated with each AE was calculated by multiplying the estimated incidence rate by the relevant treatment cost. All AEs were assumed to occur during the first cycle of treatment. Detailed incidence rates for each AE are documented in Table 1 . Table 1 Key clinical input data(China) Parameters Baseline value Range Distribution Reference Minimum Maximum Survival model for OS Tislelizumab plus chemotherapy Shape = 1.676 Scale = 16.410 Loglogistic [14] Placebo plus chemotherapy Shape = 2.283 Scale = 13.705 Loglogistic [14] Survival model for PFS Tislelizumab plus chemotherapy mu = 1.5207 sigma = 0.9659 Q= -0.6474 Gengamma [14] Placebo plus chemotherapy Shape = 3.864 Scale = 4.564 Loglogistic [14] Drug cost, $/per cycle Cost of Tislelizumab 355.78 284.62 426.94 Gamma Local charge Cost of Carboplatin 51.26 41.01 61.51 Gamma Local charge Cost of Cisplatin 35.03 28.02 42.04 Gamma Local charge Cost of Etoposide 6.63 5.30 7.96 Gamma Local charge Cost of Topotecan 246.69 197.35 296.03 Gamma Local charge Cost of the laboratory test 92.99 74.39 111.59 Gamma [24] PET-CT 912.28 729.82 1094.74 Gamma [24] Cost of end-of-life 1460.30 1168.24 1752.36 Gamma [25, 26] Best supportive care 345.60 276.48 414.72 Gamma [25] Cost of drug administration per unit Preventive medication per intravenous administration 93.93 75.14 112.72 Gamma [25, 26] Infusion fee per intravenous administration 1.86 1.49 2.23 Gamma [25, 26] Preventive medication 39.14 31.31 46.97 Gamma [25, 26] Proportion of receiving subsequent treatment Tislelizumab plus chemotherapy group 59.91% 32.40% 71.89% Beta [14] Placebo plus chemotherapy 73.91% 38.72% 88.69% Beta [14] Cost of AEs, $ Anaemia 138.75 112.32 166.50 Gamma [24] Decreased platelet count 1505.92 1219.06 1807.10 Gamma [24] Decreased neutrophil count 115.01 80.92 138.01 Gamma [24] Utilities Utility of PFS 0.69 0.63 0.78 Beta [30] Utility of PD 0.60 0.54 0.66 Beta [30] Disutility estimates Anemia 0.073 0.058 0.088 Beta [24] Decreased platelet count 0.05 0.04 0.06 Beta [24] Decreased neutrophil count 0.2 0.16 0.24 Beta [24] Risk for main AEs in Tislelizumab plus Chemotherapy group Anemia 16.30% 13.04% 19.56% Beta [14] Decreased platelet count 3.52% 2.82% 4.22% Beta [14] Decreased neutrophil count 55.95% 44.76% 67.14% Beta [14] Risk for main AEs in Placebo plus Chemotherapy group Anemia 16.59% 13.27% 19.91% Beta [14] Decreased platelet count 3.49% 2.79% 4.19% Beta [14] Decreased neutrophil count 54.59% 43.67% 65.51% Beta [14] Discount rate(China) 5% 4.00% 6.00% Beta BMI/m2 1.72 Weight/kg 65 $ 1 = ¥7.0467 38,042.49 OS: overall survival, PFS: progression-free survival, PD: progression disease, AE: adverse event, BMI: body mass index. Model structure The model outcome was developed and analyzed using TreeAge Pro 2022 software (Williamstown, MA, USA) and R software (version 4.2.3, Vienna, Austria). The model incorporated a three-state Markov model consisting of three health states: PFS, progressive disease (PD), and death (Fig. 1 ). The simulation spanned a decade, covering more than 99% of mortality events in both treatment cohorts. The analysis was conducted from the perspectives of both US and Chinese healthcare payers. In the US, this included considerations for public insurance, private insurance, and out-of-pocket payments [18]; in China, it was the entire healthcare system. Outcomes The primary outcomes assessed were quality-adjusted life years (QALYs) and costs, expressed in US dollars. Both costs and utilities were discounted annually at 3% in the US and 5% in China [19, 20]. In China, costs were updated to 2023 figures using the local consumer price index and converted to US dollars at an exchange rate of $ 1 = ¥7.0467. The study conducted a cost-effectiveness analysis, presenting the results in terms of incremental cost-effectiveness ratios (ICERs). The ICER was determined using the formula: ICER = [Cost (tislelizumab plus chemotherapy) - Cost (placebo plus chemotherapy)] / [QALY (tislelizumab plus chemotherapy) - QALY (placebo plus chemotherapy)]. The willingness-to-pay (WTP) threshold was set at three times the per capita gross domestic product (GDP) of China for 2023, amounting to $ 38,042.49, and $ 150,000.00 for the US, according to the recommendations of the World Health Organization (WHO) [21, 22]. This analysis also included the incremental net health benefit (INHB) and the incremental net monetary benefit (INMB), calculated as follows: INHB (λ) = (µE1 - µE0) - (µC1 - µC0) / λ = ΔE - ΔC / λ and INMB (λ) = (µE1 - µE0) × λ - (µC1 - µC0) = ΔE × λ - ΔC, where µCi and µEi are the costs and utility values associated with the tislelizumab plus chemotherapy regimens (i = 1) or placebo plus chemotherapy (i = 0) regimens, and λ represents the WTP threshold. Clinical data input Survival curves for OS and PFS in the RATIONALE-312 trial were constructed using a published method [23]. Time-to-event data for the Kaplan-Meier survival curves for OS and PFS were extracted using GetData Graph Digitizer ( www.getdata.graph.digitizer.com , version 2.26). These data points were subsequently used to fit various parametric survival models, including Exponential, Weibull, WeibullPH, Gamma, Log-normal, Gompertz, Generalized Gamma, and Log-logistic distributions. The selection of the most appropriate survival curves for PFS and OS was based on evaluations using the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC), complemented by a visual review of the curves, as shown in Supplemental Table 1 . Table 1 details the estimated shape parameters ( g ) and scale parameters ( λ ) for these models. Details on the long-term survival data are provided in Table 1 and illustrated in Figs. 2 – 3 . Cost input Only direct medical costs were considered, including drug expenses, laboratory test fees, PET-CT scan costs, prophylactic medications for each intravenous administration, best supportive care, end-of-life expenses, drug administration costs, subsequent treatment costs, and expenses to manage grade 3 and 4 AEs. Drug costs were obtained from public databases and local pricing schedules, while other cost data were derived from previously published studies and the relevant literature. Doses for the drugs were set according to the RATIONALE-312 study protocol. The costs per treatment cycle were calculated based on these doses and local pricing (Tables 1 – 2 ) [24–26][27][28, 29]. The costs associated with each AE were estimated by multiplying the incidence rate of the AE by the cost per occurrence of managing these events. Table 2 Key clinical input data(US) Parameters Baseline value Range Distribution Reference Minimum Maximum Drug cost, $/per cycle Cost of Tislelizumab 2554.28 2043.42 3065.14 Gamma [27] Cost of Carboplatin 55.83 44.66 67.00 Gamma [27] Cost of Cisplatin 45.79 36.63 54.95 Gamma [27] Cost of Etoposide 62.76 50.21 75.31 Gamma [27] Cost of Topotecan 2720.26 2176.208 3264.312 Gamma [27] Cost of the laboratory test 111.65 89.32 133.98 Gamma [27] PET-CT 1769.89 1415.91 2123.87 Gamma [27] Cost of end-of-life 21603.00 17282.40 25923.60 Gamma [28] Best supportive care 1447.79 1158.23 1737.35 Gamma [28] Cost of drug administration first hour 142.55 114.04 171.06 Gamma [29] Administration intravenous, additional hour 30.68 24.54 36.82 Gamma [29] Cost of AEs, $ Anaemia 7941.00 6352.80 9529.20 Gamma [28] Decreased platelet count 13105.00 10484.00 15726.00 Gamma [28] Decreased neutrophil count 13105.00 10484.00 15726.00 Gamma [28] Discount rate 3% 4.00% 6.00% Beta BMI/m2 1.79 Weight/kg 65 AE: adverse event, BMI: body mass index. Quality-of-life inputs Health utility scores were assigned on a scale from death (0) to perfect health (1). Due to the lack of data on the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) from the RATIONALE-312 trial, direct quality-of-life data were unavailable. Consequently, utility values were adopted from the existing literature (Table 1 ). The utility values for PFS and PD were set at 0.69 and 0.60, respectively [30]. AEs were assumed to reduce health utility, a concept known as disutility. This disutility associated with AEs was incorporated only in the first cycle of the model and was considered to occur once every three weeks. Scenario analysis Given the high uncertainty about the model assumptions and the sources of the parameters in this research, scenario analyses were performed. For the US, without prior data on the price of tislelizumab, a price equivalent to that in Hong Kong ( $ 1,277.14 per 100 mg) was used in the base-case analysis. The price varied between $ 0 and $ 5,000 to examine the potential cost-effectiveness under the WTP threshold of $ 150,000. Sensitivity analysis One-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were conducted to evaluate the inherent uncertainty of the model. In the OWSA, the parameter range was derived from the existing literature, defined by 95% CIs or a ± 20% variation from baseline values. For PSA, the model parameters were varied simultaneously across 10,000 Monte Carlo simulations to assess the probability that each intervention was cost-effective, considering different WTP thresholds for an additional QALY. These simulations modeled utility parameters using beta distributions, while cost variables used gamma distributions. The results of these analyses are shown in a scatter plot and a cost-effectiveness acceptability curve. Results Base-case analysis During a 10-year analysis horizon, base-case results indicated that the tislelizumab plus chemotherapy group accrued an additional 0.96 QALYs at an incremental cost of $ 25,314.16. The chemotherapy-only group gained 0.69 QALYs with associated costs of $ 16,961.98. Comparative analysis showed a mean incremental effect of 0.27 QALYs at an additional cost of $ 8,352.18 for the tislelizumab group. This resulted in an ICER of $ 31,136.52 per QALY for tislelizumab plus chemotherapy compared to chemotherapy alone ( Supplemental Table 2 ). When evaluated against China’s WTP threshold of $ 38,042.49 per QALY, tislelizumab plus chemotherapy was more cost-effective than chemotherapy alone. The INHB was 0.05 QALYs, and the INMB was $ 1,852.49 ( Supplemental Table 2 ). In the US, the ICER for tislelizumab plus chemotherapy was $ 157,117.67 per QALY, exceeding the US WTP threshold of $ 150,000.00 per QALY ( Supplemental Table 2 ). Additionally, INHB was − 0.01 QALYs, and INMB was - $ 2,045.70, compared to chemotherapy alone at the $ 150,000.00 WTP threshold ( Supplemental Table 2 ). Price simulation The results of the price simulation, shown in Fig. 4 , reveal that in the US since the price of tislelizumab ranged between $ 0 and $ 5,000.00 per 100 mg, the ICER increased accordingly. Tislelizumab was cost-effective when priced below $ 1,199.38 per 100 mg, adhering to the WTP threshold of $ 150,000.00. Sensitivity analysis Supplemental Fig. 1 shows a tornado diagram from OWSA that analyzes the entire population. This diagram identifies the most influential factors on the base-case outcomes: the cost of tislelizumab, the utility value of PFS, and the cost of PET-CT scans. Supplemental Fig. 2 highlights that for US patients, ICER was mainly affected by the cost of tislelizumab, the proportion of patients in the tislelizumab plus chemotherapy group receiving subsequent systemic treatment, and the proportion in the placebo plus chemotherapy group receiving similar treatment. However, due to the minimal differences in health outcomes between the two treatment strategies between the two groups, various changes in parameter values significantly affected the study results. Supplemental Figs. 3–6 , featuring acceptability curves and probabilistic scatter plots, offer a practical and visual representation of the cost-effectiveness landscape. These tools, which are crucial for decision-making, elucidate the probabilities that tislelizumab plus chemotherapy is considered cost-effective. PSA results indicate substantial probabilities, with rates of 86.49% in China and 44.07% in the US, corresponding to a WTP threshold of three times China’s GDP per capita ( $ 38,042.49) and $ 150,000.00 in the US. Discussion The RATIONALE-312 trial demonstrated that adding tislelizumab to chemotherapy significantly improved OS and other key efficacy outcomes in patients with ES-SCLC[14]. Although tislelizumab has been approved in China and the FDA has granted orphan drug status for SCLC, its high potential to reshape the global immunotherapy market for ES-SCLC is tempered by limited price information. This uncertainty poses a dilemma for physicians and patients in determining its cost-effectiveness, which requires a thorough economic analysis. Based on the RATIONALE-312 trial, our economic analysis from the Chinese healthcare perspective shows that tislelizumab plus chemotherapy resulted in an ICER of $ 31,136.52 per QALY, below the WTP threshold of $ 38,042.49 per QALY. However, from the US perspective, the ICER reaches $ 157,117.67 per QALY, exceeding the US WTP threshold of $ 150,000.00. This analysis is further supported by the INHB and INMB findings, indicating INHBs of 0.05 and − 0.01 and INMBs of $ 1,852.49 and - $ 2,045.70, respectively, for the Chinese and US settings compared to chemotherapy alone. Previous studies have indicated that most immune checkpoint inhibitors combined with chemotherapy are not cost-effective as first-line therapy for patients with ES-SCLC [28, 29, 31–35]. Common in these studies is the finding that the cost of PD-L1 antibodies significantly impacts outcomes. For example, in the US, the ICER for tislelizumab plus chemotherapy approximates the WTP threshold of $ 150,000.00 per QALY. The cost-effectiveness acceptability curve aligns with this, showing a 44.07% probability that this combination is cost-effective at a threshold of three times the GDP per capita per QALY. Sensitivity analyses confirm these results, with minor differences in health outcomes between the two strategies that significantly alter study results. In particular, we assumed that the price of tislelizumab was the same as in Hong Kong ( $ 1,277.14 per 100 mg), which does not reflect its price in the United States. However, price simulations indicate that tislelizumab is favored when priced below $ 1,199.38 per 100 mg at the $ 150,000.00 WTP threshold. This study is the first to evaluate the cost-effectiveness of tislelizumab plus chemotherapy as first-line therapy for ES-SCLC from both the US and China perspectives. It offers information to US decision-makers on the pricing of tislelizumab should they consider supporting its entry into the US market. Additionally, due to the absence of quality of life (EQ-5D) and cost per QALY data in the RATIONALE-312 trial, we rely on utility values from the literature for PFS and PD. This approach, while necessary, introduces uncertainties in our modeled results. Importantly, unlike many studies that derive quality of life and health utility data from non-small cell lung cancer (NSCLC), our study uses data specifically from SCLC studies, enhancing the relevance and accuracy of our findings. This analysis has several limitations. First, clinical data were sourced from a phase 3 trial conducted in China, while cost-effectiveness analysis was performed from the perspective of US payers, which could introduce geographic bias. Second, the range of options for second-line treatments, such as chemotherapy, targeted therapy, immunotherapy, and radiation therapy, is complex and varied. Due to the absence of specific drug information in the corresponding clinical trials, assumptions were made about subsequent chemotherapy and the best supportive care. Third, this study did not account for the management costs and disutility associated with grade 1–2 AEs. Given that the tislelizumab plus chemotherapy arm experienced a higher incidence of such AEs than the chemotherapy arm, this oversight might underestimate ICER. Despite these challenges, conducting a cost-effectiveness analysis based on data from the RATIONALE-312 study is still feasible and provides critical information for treatment decision-making. Conclusions This investigation reveals that combining tislelizumab with chemotherapy represents a cost-effective first-line treatment for patients with ES-SCLC within the Chinese healthcare system. However, this combination does not meet the same cost-effectiveness criteria in the US healthcare system. This analysis offers valuable guidance to decision-makers and healthcare professionals, providing robust evidence to support the expanded use of tislelizumab in clinical practices globally. Declarations Acknowledgments None Funding This work was supported by Drug clinical comprehensive evaluation project of Health Commission of Guangxi Zhuang Autonomous Region(Grant No. YPPJ014). Conflicts of interest The authors declare that they have no conflicts of interest. References Sung H, Ferlay J, Siegel RL et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49. https://doi.org/10.3322/caac.21660. Oronsky B, Abrouk N, Caroen S et al. A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC). J Cancer. 2022;13(9):2945-53. https://doi.org/10.7150/jca.75622. Rudin CM, Brambilla E, Faivre-Finn C et al. Small-cell lung cancer. Nat Rev Dis Primers. 2021;7(1):3. https://doi.org/10.1038/s41572-020-00235-0. Sathiyapalan A, Febbraro M, Pond GR et al. Chemo-Immunotherapy in First Line Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Systematic Review and Meta-Analysis. Curr Oncol. 2022;29(12):9046-65. https://doi.org/10.3390/curroncol29120709. Paz-Ares L, Dvorkin M, Chen Y et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-39. https://doi.org/10.1016/s0140-6736(19)32222-6. Rudin CM, Ismaila N, Hann CL et al. Treatment of Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline. J Clin Oncol. 2015;33(34):4106-11. https://doi.org/10.1200/jco.2015.63.7918. Rossi A, Di Maio M, Chiodini P et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol. 2012;30(14):1692-8. https://doi.org/10.1200/jco.2011.40.4905. Wang J, Zhou C, Yao W et al. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23(6):739-47. https://doi.org/10.1016/s1470-2045(22)00224-8. Horn L, Mansfield AS, Szczęsna A et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018;379(23):2220-9. https://doi.org/10.1056/NEJMoa1809064. Paz-Ares L, Chen Y, Reinmuth N et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7(2):100408. https://doi.org/10.1016/j.esmoop.2022.100408. Liu SV, Reck M, Mansfield AS et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021;39(6):619-30. https://doi.org/10.1200/jco.20.01055. Cheng Y, Han L, Wu L et al. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial. Jama. 2022;328(12):1223-32. https://doi.org/10.1001/jama.2022.16464. Zhang T, Song X, Xu L et al. The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions. Cancer Immunol Immunother. 2018;67(7):1079-90. https://doi.org/10.1007/s00262-018-2160-x. Cheng Y, Fan Y, Zhao Y et al. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024. https://doi.org/10.1016/j.jtho.2024.03.008. Husereau D, Drummond M, Augustovski F et al. Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) Statement: Updated Reporting Guidance for Health Economic Evaluations. Value Health. 2022;25(1):3-9. https://doi.org/10.1016/j.jval.2021.11.1351. Ganti AKP, Loo BW, Bassetti M et al. Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19(12):1441-64. https://doi.org/10.6004/jnccn.2021.0058. Goulart B, Ramsey S. A trial-based assessment of the cost-utility of bevacizumab and chemotherapy versus chemotherapy alone for advanced non-small cell lung cancer. Value Health. 2011;14(6):836-45. https://doi.org/10.1016/j.jval.2011.04.004. Dieleman JL, Cao J, Chapin A et al. US Health Care Spending by Payer and Health Condition, 1996-2016. Jama. 2020;323(9):863-84. https://doi.org/10.1001/jama.2020.0734. Su D, Wu B, Shi L. Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma. JAMA Netw Open. 2021;4(2):e210037. https://doi.org/10.1001/jamanetworkopen.2021.0037. Yue X, Li Y, Wu J et al. Current Development and Practice of Pharmacoeconomic Evaluation Guidelines for Universal Health Coverage in China. Value Health Reg Issues. 2021;24:1-5. https://doi.org/10.1016/j.vhri.2020.07.580. Murray CJ, Evans DB, Acharya A et al. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ. 2000;9(3):235-51. https://doi.org/10.1002/(sici)1099-1050(200004)9:33.0.co;2-o. Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness--the curious resilience of the $50,000-per-QALY threshold. N Engl J Med. 2014;371(9):796-7. https://doi.org/10.1056/NEJMp1405158. Guyot P, Ades AE, Ouwens MJ et al. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2012;12:9. https://doi.org/10.1186/1471-2288-12-9. Zhu Y, Liu K, Qin Q et al. Serplulimab plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: A cost-effectiveness analysis. Front Immunol. 2022;13:1044678. https://doi.org/10.3389/fimmu.2022.1044678. Liu L, Wang L, Chen L et al. Cost-effectiveness of sintilimab plus chemotherapy versus chemotherapy alone as first-line treatment of locally advanced or metastatic oesophageal squamous cell carcinoma. Front Immunol. 2023;14:1092385. https://doi.org/10.3389/fimmu.2023.1092385. Cao X, Cai H, Li N et al. First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone for advanced esophageal cancer: a cost-effectiveness analysis. Ther Adv Med Oncol. 2022;14:17588359221122733. https://doi.org/10.1177/17588359221122733. Centers for Medicare and Medicaid Services. Medicare Physician Fee Schedule Look-Up Tool (2021). Available at: https://www.cms.gov/medicare/physicianfee-schedule/search (Accessed 11January 2021) Shao T, Zhao M, Liang L et al. Serplulimab Plus Chemotherapy vs Chemotherapy for Treatment of US and Chinese Patients with Extensive-Stage Small-Cell Lung Cancer: A Cost-Effectiveness Analysis to Inform Drug Pricing. BioDrugs. 2023;37(3):421-32. https://doi.org/10.1007/s40259-023-00586-6. Liu Q, Luo X, Yi L et al. First-Line Chemo-Immunotherapy for Extensive-Stage Small-Cell Lung Cancer: A United States-Based Cost-Effectiveness Analysis. Front Oncol. 2021;11:699781. https://doi.org/10.3389/fonc.2021.699781. Vedadi A, Shakik S, Brown MC et al. The impact of symptoms and comorbidity on health utility scores and health-related quality of life in small cell lung cancer using real world data. Qual Life Res. 2021;30(2):445-54. https://doi.org/10.1007/s11136-020-02615-1. Long Y, Xu Y, Liao L et al. Cost-effectiveness analysis of serplulimab combined with chemotherapy in the treatment of extensive-stage small-cell lung cancer from the perspective of the healthcare system in China. BMJ Open. 2023;13(8):e072106. https://doi.org/10.1136/bmjopen-2023-072106. Zhou K, Zhou J, Huang J et al. Cost-effectiveness analysis of atezolizumab plus chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer. Lung Cancer. 2019;130:1-4. https://doi.org/10.1016/j.lungcan.2019.01.019. Xiang G, Jiang T, Gan L et al. Cost-effectiveness of serplulimab as first-line therapy for extensive-stage small cell lung cancer in China. Front Immunol. 2023;14:1223020. https://doi.org/10.3389/fimmu.2023.1223020. Wang Y, Rui M, Yang L et al. Economic Evaluation of First-Line Atezolizumab for Extensive-Stage Small-Cell Lung Cancer in the US. Front Public Health. 2021;9:650392. https://doi.org/10.3389/fpubh.2021.650392. Ding D, Hu H, Li S et al. Cost-Effectiveness Analysis of Durvalumab Plus Chemotherapy in the First-Line Treatment of Extensive-Stage Small Cell Lung Cancer. J Natl Compr Canc Netw. 2021;19(10):1141-7. https://doi.org/10.6004/jnccn.2020.7796. Supplementary Files SupplFigure12tornado.docx SupplFigure34acceptability.docx SupplFigure56scatterplot.docx SupplTable1AICBIC.docx SupplTable2baseanalysis.docx Cite Share Download PDF Status: Published Journal Publication published 14 Sep, 2024 Read the published version in International Journal of Clinical Pharmacy → Version 1 posted Editorial decision: Major revisions 12 Jun, 2024 Reviewers agreed at journal 25 May, 2024 Reviewers invited by journal 25 May, 2024 Editor invited by journal 22 May, 2024 Editor assigned by journal 21 May, 2024 First submitted to journal 20 May, 2024 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. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4451605","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":306680074,"identity":"811da31c-cb5f-4fcc-ae22-0399057b93e4","order_by":0,"name":"Wenwang Lang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYBACfvbG9h8JFRJy/OwNRGqR7Dl8QOLDGRtjyZ4DRGoxuJGWIDmzLS3R4EYCsS67kWNgzMN2OIHh5uONNxhqbKIJ6mDseWOQzMNzOI9xdlqxBcOxtNwGQlqY2XMMDvNIHC5mls4xk2BsOExYCxtDjmEzj8HhxDbJM0Rq4eFIS2ackZCW2CPBQ6QWCZ7Dxxg+HLAxluAB+iWBGL/YH29sY0j8JyFnf/zwxhsfamwIa0EGBhIJpCiHaCFVxygYBaNgFIwMAAAUqUEKo8IZ5gAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0007-3583-9518","institution":"Second Peoples Hospital of Guangxi Zhuang Autonomous Region: Nanxishan Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":true,"prefix":"","firstName":"Wenwang","middleName":"","lastName":"Lang","suffix":""},{"id":306680075,"identity":"019336bb-eedd-4b2e-97b0-1fd77a28c9a8","order_by":1,"name":"Qi Ai","email":"","orcid":"","institution":"Second Peoples Hospital of Guangxi Zhuang Autonomous Region: Nanxishan Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Ai","suffix":""},{"id":306680076,"identity":"d86984ba-d13f-4664-9ffd-8a19c00464f5","order_by":2,"name":"Yulong He","email":"","orcid":"","institution":"Second Peoples Hospital of Guangxi Zhuang Autonomous Region: Nanxishan Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Yulong","middleName":"","lastName":"He","suffix":""},{"id":306680077,"identity":"8e56f138-83ca-483f-918d-4b4635baf1c3","order_by":3,"name":"Yufei Pan","email":"","orcid":"","institution":"Second Peoples Hospital of Guangxi Zhuang Autonomous Region: Nanxishan Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Yufei","middleName":"","lastName":"Pan","suffix":""},{"id":306680078,"identity":"ab760127-eace-4109-9af5-fa93cfd59461","order_by":4,"name":"Qinling Jiang","email":"","orcid":"","institution":"Second Peoples Hospital of Guangxi Zhuang Autonomous Region: Nanxishan Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Qinling","middleName":"","lastName":"Jiang","suffix":""},{"id":306680079,"identity":"fb860dae-f77a-483c-8b22-a630598bc8e6","order_by":5,"name":"Ming Ouyang","email":"","orcid":"","institution":"Second Peoples Hospital of Guangxi Zhuang Autonomous Region: Nanxishan Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Ouyang","suffix":""},{"id":306680080,"identity":"75ea4ec3-9a37-4712-aa23-abdb99310d4c","order_by":6,"name":"Tianshou Sun","email":"","orcid":"","institution":"Second Peoples Hospital of Guangxi Zhuang Autonomous Region: Nanxishan Hospital of Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Tianshou","middleName":"","lastName":"Sun","suffix":""}],"badges":[],"createdAt":"2024-05-21 02:10:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4451605/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4451605/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11096-024-01802-1","type":"published","date":"2024-09-14T15:57:41+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":58144681,"identity":"86045b27-2fb9-4f63-bdab-85816bf2b002","added_by":"auto","created_at":"2024-06-11 18:26:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":126864,"visible":true,"origin":"","legend":"\u003cp\u003eModel structure\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4451605/v1/b6cfc4dda7173be1ef8cb354.png"},{"id":58145819,"identity":"bcfb2224-50b0-41ca-8cd2-befedf2f5d89","added_by":"auto","created_at":"2024-06-11 18:34:04","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":22248,"visible":true,"origin":"","legend":"\u003cp\u003eThe Kaplan-Meier overall survival curves\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4451605/v1/0caa184d53d120e5706dd233.png"},{"id":58144680,"identity":"9b750d7f-c977-468f-84b7-a519d487f221","added_by":"auto","created_at":"2024-06-11 18:26:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":19813,"visible":true,"origin":"","legend":"\u003cp\u003eThe Kaplan-Meier progression-free survival curves\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-4451605/v1/c9c8f6f794bfa41891015c2c.png"},{"id":58144684,"identity":"ae9bd188-f420-4318-86f0-aa3af021ce7a","added_by":"auto","created_at":"2024-06-11 18:26:04","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":211845,"visible":true,"origin":"","legend":"\u003cp\u003ePrice Simulation of The US\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-4451605/v1/aeffd1224862db160ccbd4e0.png"},{"id":64619531,"identity":"18a742d5-556f-4e14-b51e-409da3fb34fe","added_by":"auto","created_at":"2024-09-16 16:15:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1081667,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4451605/v1/b5f1bbf5-b98d-4274-a3a1-28707ee8bda1.pdf"},{"id":58144689,"identity":"ca4e1b7c-f5e6-43f6-b552-c5091a3f3226","added_by":"auto","created_at":"2024-06-11 18:26:05","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":248226,"visible":true,"origin":"","legend":"","description":"","filename":"SupplFigure12tornado.docx","url":"https://assets-eu.researchsquare.com/files/rs-4451605/v1/faa81fe212553b273a5d775c.docx"},{"id":58145820,"identity":"1b79eef2-2c00-46b5-bc75-21f5263a38b4","added_by":"auto","created_at":"2024-06-11 18:34:04","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":171096,"visible":true,"origin":"","legend":"","description":"","filename":"SupplFigure34acceptability.docx","url":"https://assets-eu.researchsquare.com/files/rs-4451605/v1/650c79e209ee12884b9a48fe.docx"},{"id":58144688,"identity":"5951e7eb-f635-4ae5-86b3-9afd6b1ed986","added_by":"auto","created_at":"2024-06-11 18:26:04","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":280904,"visible":true,"origin":"","legend":"","description":"","filename":"SupplFigure56scatterplot.docx","url":"https://assets-eu.researchsquare.com/files/rs-4451605/v1/db067a9f8ce3e4cabc649e15.docx"},{"id":58144687,"identity":"6e06ded9-1b1c-4a1d-a4bf-af38cd33326e","added_by":"auto","created_at":"2024-06-11 18:26:04","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":15597,"visible":true,"origin":"","legend":"","description":"","filename":"SupplTable1AICBIC.docx","url":"https://assets-eu.researchsquare.com/files/rs-4451605/v1/7643b7a57baa10faf4cca2be.docx"},{"id":58144686,"identity":"bf53a3e4-ef91-44a7-86cd-d31763f53a59","added_by":"auto","created_at":"2024-06-11 18:26:04","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":14196,"visible":true,"origin":"","legend":"","description":"","filename":"SupplTable2baseanalysis.docx","url":"https://assets-eu.researchsquare.com/files/rs-4451605/v1/d4421e83bf468bfbf3988959.docx"}],"financialInterests":"","formattedTitle":"Comparative cost-effectiveness of tislelizumab plus chemotherapy versus standard chemotherapy in first-line treatment for extensive-stage small cell lung cancer: perspectives from the U.S. and Chinese healthcare systems","fulltext":[{"header":"Impact statements","content":"\u003cul type=\"disc\"\u003e\n \u003cli\u003eThis study is the first to evaluate the cost-effectiveness of tislelizumab plus chemotherapy as first-line therapy for ES-SCLC from both the US and China perspectives.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTislelizumab with chemotherapy may be a cost-effective first-line treatment option for ES-SCLC in China, but not meet the same cost-effectiveness criteria in the US healthcare system.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eLung cancer remains the leading cause of cancer-related mortality worldwide and is the second most common cancer diagnosed [1\u0026ndash;3]. Small cell lung cancer (SCLC) accounts for about 15% of all lung cancer cases and is marked by its highly aggressive nature and the tendency to early metastasis. Most SCLC patients (80\u0026ndash;85%) are identified with extensive-stage disease (ES-SCLC), which is associated with a poor prognosis. For decades, platinum-based chemotherapy combinations have been the cornerstone of first-line treatment for ES-SCLC, but survival rates remain inadequate [4, 5]. Despite initial sensitivity to chemotherapy, almost all patients with ES-SCLC relapse within 6 months, leading to a bleak 5-year survival rate of less than 5% [6, 7].\u003c/p\u003e \u003cp\u003eAlthough initial progress was slow, the introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the therapeutic landscape for ES-SCLC. Three phase III trials incorporating atezolizumab, durvalumab, or adebrelimab with chemotherapy have shown significant improvements in overall survival (OS) benefits [8\u0026ndash;11]. A global randomized phase III trial (ASTRUM-005) demonstrated that the combination of the anti-PD-1 antibody serplulimab with chemotherapy substantially extended progression-free survival (PFS) and OS [12].\u003c/p\u003e \u003cp\u003eTislelizumab, a PD-L1/PD-L2 signaling antagonist, has demonstrated the potential to increase cytokine production and reactivate T cell function, contributing to immune-mediated tumor cell destruction[13]. In the RATIONALE-312 study [14], tislelizumab combined with chemotherapy produced a statistically significant OS advantage over placebo combined with chemotherapy (stratified hazard ratio [HR]\u0026thinsp;=\u0026thinsp;0.75 [95% confidence ratio (CI): 0.61\u0026ndash;0.93]; one-sided p\u0026thinsp;=\u0026thinsp;0.0040; median: 15.5 [95% CI: 13.5\u0026ndash;17.1] months versus 13.5 months [95% CI: 12.1\u0026ndash;14.9], respectively). Additionally, PFS significantly favored the tislelizumab group (stratified HR\u0026thinsp;=\u0026thinsp;0.64 [95% CI: 0.52\u0026ndash;0.78]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; median: 4.7 [95% CI: 4.3\u0026ndash;5.5] months versus 4.3 months [95% CI: 4.2\u0026ndash;4.4], respectively). Grade\u0026thinsp;\u0026ge;\u0026thinsp;3 treatment-related adverse events, mainly hematologic, occurred in 86% of the participants in both treatment arms.\u003c/p\u003e \u003cp\u003eThe advent of tislelizumab may potentially shape the treatment markets for ES-SCLC in both the US and China with first-line ICIs. Tislelizumab is expected to be the first anti-PD-1 antibody approved globally. Despite these promising clinical outcomes, the financial implications of this combination therapy, which is more expensive than chemotherapy alone, cannot be overlooked. The cost of tislelizumab in China is approximately \u003cspan\u003e$\u003c/span\u003e400 per cycle (21 days), compared to \u003cspan\u003e$\u003c/span\u003e60 for the standard chemotherapy regimen, suggesting a possible need for price adjustments. Meanwhile, the price of tislelizumab in the US remains undisclosed. This study aimed to evaluate the cost-effectiveness of tislelizumab combined with chemotherapy versus chemotherapy alone as first-line treatment for previously untreated ES-SCLC patients from the perspective of US and Chinese healthcare payers to guide drug pricing strategies.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\"\u003e\n \u003ch2\u003ePatients and intervention\u003c/h2\u003e\n \u003cp\u003eThis study was conducted according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist [15]. Participants were required to be 18 years or older and have histologically or cytologically ES-SCLC, determined by expert pathologists and defined by the Seventh Edition of the American Joint Committee on Cancer (AJCC) as Stage IV (T any, N any, M1a or M1b), or T3-4 due to multiple lung nodules that were too widespread, or with a tumor or nodal volume too large to be included in a tolerable irradiation plan. Patients had to have an Eastern Cooperative Oncology Group (ECOG) performance status\u0026thinsp;\u0026le;\u0026thinsp;1, a life expectancy\u0026thinsp;\u0026ge;\u0026thinsp;12 weeks, adequate organ function, and no previous systemic treatment for ES-SCLC.\u003c/p\u003e\n \u003cp\u003eThe induction phase included four 21-day cycles of intravenous tislelizumab 200 mg or placebo administered every three weeks (Q3W), combined with etoposide (100 mg/m\u0026sup2; intravenously on days 1\u0026ndash;3 of each cycle) and carboplatin (area under the plasma or serum concentration-time curve\u0026thinsp;=\u0026thinsp;5) on the first day of each cycle. After the induction phase, maintenance therapy with 200 mg intravenous tislelizumab or placebo Q3W continued until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent. Tumor imaging, including Positron Emission Tomography-Computed Tomography (PET-CT) scan, every 6 weeks (\u0026plusmn;\u0026thinsp;7 days) for the first 48 weeks following the first day of treatment, and every 9 weeks (\u0026plusmn;\u0026thinsp;7 days) after that.\u003c/p\u003e\n \u003cp\u003eA total of 306 patients (67%) received additional systemic anticancer treatments after discontinuing the study medications: 136 patients (60%) from the tislelizumab group and 170 patients (74%) from the placebo group. The most prevalent treatments in both groups were conventional chemotherapies, utilized by 124 patients (55%) in the tislelizumab group and 155 patients (67%) in the placebo group. The selection of chemotherapies, not fully specified, followed recommendations from the National Comprehensive Cancer Network (NCCN)[16], the Chinese Society of Clinical Oncology (CSCO) guidelines, findings from the RATIONALE-312 trial, and general clinical practice. Subsequent therapies included combinations such as topotecan with cisplatin or simply the best supportive care. The body surface area and creatinine clearance rates were assumed to be similar to those reported in previous studies [17].\u003c/p\u003e\n \u003cp\u003eThe cost implications of adverse events (AEs) were assessed using data from the RATIONALE-312 trial. Our analysis focused exclusively on serious adverse events (SAEs) of grade 3 or 4 with an incidence rate greater than 3%. These SAEs included anemia, reduced platelet count, and decreased neutrophil count. The cost associated with each AE was calculated by multiplying the estimated incidence rate by the relevant treatment cost. All AEs were assumed to occur during the first cycle of treatment. Detailed incidence rates for each AE are documented in Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eKey clinical input data(China)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eBaseline value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDistribution\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMinimum\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMaximum\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eSurvival model for OS\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTislelizumab plus chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShape\u0026thinsp;=\u0026thinsp;1.676\u003c/p\u003e\n \u003cp\u003eScale\u0026thinsp;=\u0026thinsp;16.410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLoglogistic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003ePlacebo plus chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShape\u0026thinsp;=\u0026thinsp;2.283\u003c/p\u003e\n \u003cp\u003eScale\u0026thinsp;=\u0026thinsp;13.705\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLoglogistic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eSurvival model for PFS\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTislelizumab plus chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emu\u0026thinsp;=\u0026thinsp;1.5207\u003c/p\u003e\n \u003cp\u003esigma\u0026thinsp;=\u0026thinsp;0.9659\u003c/p\u003e\n \u003cp\u003eQ= -0.6474\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGengamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003ePlacebo plus chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShape\u0026thinsp;=\u0026thinsp;3.864\u003c/p\u003e\n \u003cp\u003eScale\u0026thinsp;=\u0026thinsp;4.564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLoglogistic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eDrug cost, $/per cycle\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCost of Tislelizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e355.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e284.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e426.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocal charge\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCost of Carboplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocal charge\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCost of Cisplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocal charge\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCost of Etoposide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocal charge\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCost of Topotecan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e246.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e197.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e296.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocal charge\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCost of the laboratory test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003ePET-CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e912.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e729.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1094.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCost of end-of-life\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1460.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1168.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1752.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[25, 26]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eBest supportive care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e345.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e276.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e414.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[25]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eCost of drug administration per unit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreventive medication per intravenous administration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e112.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[25, 26]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInfusion fee per intravenous administration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[25, 26]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreventive medication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[25, 26]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eProportion of receiving subsequent treatment\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTislelizumab plus chemotherapy group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.91%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.40%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.89%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003ePlacebo plus chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.91%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.72%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.69%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eCost of AEs, $\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAnaemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e138.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e112.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e166.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDecreased platelet count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1505.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1219.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1807.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDecreased neutrophil count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e115.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e138.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eUtilities\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eUtility of PFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[30]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eUtility of PD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[30]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003eDisutility estimates\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDecreased platelet count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDecreased neutrophil count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[24]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eRisk for main AEs in Tislelizumab plus Chemotherapy group\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.30%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.04%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.56%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDecreased platelet count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.52%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.82%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.22%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDecreased neutrophil count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.95%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.76%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.14%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eRisk for main AEs in Placebo plus Chemotherapy group\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.59%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.27%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.91%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDecreased platelet count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.49%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.79%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.19%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDecreased neutrophil count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.59%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.67%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.51%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[14]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDiscount rate(China)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eBMI/m2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eWeight/kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e1 = \u0026yen;7.0467\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38,042.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eOS: overall survival, PFS: progression-free survival, PD: progression disease, AE: adverse event, BMI: body mass index.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\"\u003e\n \u003ch2\u003eModel structure\u003c/h2\u003e\n \u003cp\u003eThe model outcome was developed and analyzed using TreeAge Pro 2022 software (Williamstown, MA, USA) and R software (version 4.2.3, Vienna, Austria). The model incorporated a three-state Markov model consisting of three health states: PFS, progressive disease (PD), and death (Fig.\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e). The simulation spanned a decade, covering more than 99% of mortality events in both treatment cohorts. The analysis was conducted from the perspectives of both US and Chinese healthcare payers. In the US, this included considerations for public insurance, private insurance, and out-of-pocket payments [18]; in China, it was the entire healthcare system.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\"\u003e\n \u003ch2\u003eOutcomes\u003c/h2\u003e\n \u003cp\u003eThe primary outcomes assessed were quality-adjusted life years (QALYs) and costs, expressed in US dollars. Both costs and utilities were discounted annually at 3% in the US and 5% in China [19, 20]. In China, costs were updated to 2023 figures using the local consumer price index and converted to US dollars at an exchange rate of \u003cspan\u003e$\u003c/span\u003e1 = \u0026yen;7.0467. The study conducted a cost-effectiveness analysis, presenting the results in terms of incremental cost-effectiveness ratios (ICERs). The ICER was determined using the formula: ICER = [Cost (tislelizumab plus chemotherapy) - Cost (placebo plus chemotherapy)] / [QALY (tislelizumab plus chemotherapy) - QALY (placebo plus chemotherapy)].\u003c/p\u003e\n \u003cp\u003eThe willingness-to-pay (WTP) threshold was set at three times the per capita gross domestic product (GDP) of China for 2023, amounting to \u003cspan\u003e$\u003c/span\u003e38,042.49, and \u003cspan\u003e$\u003c/span\u003e150,000.00 for the US, according to the recommendations of the World Health Organization (WHO) [21, 22]. This analysis also included the incremental net health benefit (INHB) and the incremental net monetary benefit (INMB), calculated as follows: INHB (\u0026lambda;) = (\u0026micro;E1 - \u0026micro;E0) - (\u0026micro;C1 - \u0026micro;C0) / \u0026lambda;\u0026thinsp;=\u0026thinsp;\u0026Delta;E - \u0026Delta;C / \u0026lambda; and INMB (\u0026lambda;) = (\u0026micro;E1 - \u0026micro;E0) \u0026times; \u0026lambda; - (\u0026micro;C1 - \u0026micro;C0) = \u0026Delta;E\u0026thinsp;\u0026times;\u0026thinsp;\u0026lambda; - \u0026Delta;C, where \u0026micro;Ci and \u0026micro;Ei are the costs and utility values associated with the tislelizumab plus chemotherapy regimens (i\u0026thinsp;=\u0026thinsp;1) or placebo plus chemotherapy (i\u0026thinsp;=\u0026thinsp;0) regimens, and \u0026lambda; represents the WTP threshold.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\"\u003e\n \u003ch2\u003eClinical data input\u003c/h2\u003e\n \u003cp\u003eSurvival curves for OS and PFS in the RATIONALE-312 trial were constructed using a published method [23]. Time-to-event data for the Kaplan-Meier survival curves for OS and PFS were extracted using GetData Graph Digitizer (\u003cspan\u003e\u003cspan\u003ewww.getdata.graph.digitizer.com\u003c/span\u003e\u003c/span\u003e, version 2.26). These data points were subsequently used to fit various parametric survival models, including Exponential, Weibull, WeibullPH, Gamma, Log-normal, Gompertz, Generalized Gamma, and Log-logistic distributions.\u003c/p\u003e\n \u003cp\u003eThe selection of the most appropriate survival curves for PFS and OS was based on evaluations using the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC), complemented by a visual review of the curves, as shown in \u003cstrong\u003eSupplemental Table\u0026nbsp;1\u003c/strong\u003e. Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e details the estimated shape parameters (\u003cem\u003eg\u003c/em\u003e) and scale parameters (\u003cem\u003e\u0026lambda;\u003c/em\u003e) for these models. Details on the long-term survival data are provided in Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e and illustrated in Figs.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e\u0026ndash;\u003cspan\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\"\u003e\n \u003ch2\u003eCost input\u003c/h2\u003e\n \u003cp\u003eOnly direct medical costs were considered, including drug expenses, laboratory test fees, PET-CT scan costs, prophylactic medications for each intravenous administration, best supportive care, end-of-life expenses, drug administration costs, subsequent treatment costs, and expenses to manage grade 3 and 4 AEs. Drug costs were obtained from public databases and local pricing schedules, while other cost data were derived from previously published studies and the relevant literature.\u003c/p\u003e\n \u003cp\u003eDoses for the drugs were set according to the RATIONALE-312 study protocol. The costs per treatment cycle were calculated based on these doses and local pricing (Tables\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e\u0026ndash;\u003cspan\u003e2\u003c/span\u003e) [24\u0026ndash;26][27][28, 29]. The costs associated with each AE were estimated by multiplying the incidence rate of the AE by the cost per occurrence of managing these events.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eKey clinical input data(US)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eBaseline value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDistribution\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMinimum\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMaximum\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cem\u003eDrug cost, $/per cycle\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCost of Tislelizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2554.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2043.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3065.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[27]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCost of Carboplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[27]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCost of Cisplatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[27]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCost of Etoposide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[27]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCost of Topotecan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2720.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2176.208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3264.312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[27]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCost of the laboratory test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e133.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[27]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePET-CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1769.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1415.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2123.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[27]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCost of end-of-life\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21603.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17282.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25923.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[28]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBest supportive care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1447.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1158.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1737.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[28]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCost of drug administration first hour\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e142.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e114.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e171.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[29]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdministration intravenous, additional hour\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[29]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cem\u003eCost of AEs, $\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnaemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7941.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6352.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9529.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[28]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDecreased platelet count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13105.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10484.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15726.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[28]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDecreased neutrophil count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13105.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10484.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15726.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGamma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[28]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiscount rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI/m2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeight/kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eAE: adverse event, BMI: body mass index.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003eQuality-of-life inputs\u003c/h2\u003e\n \u003cp\u003eHealth utility scores were assigned on a scale from death (0) to perfect health (1). Due to the lack of data on the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) from the RATIONALE-312 trial, direct quality-of-life data were unavailable. Consequently, utility values were adopted from the existing literature (Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e). The utility values for PFS and PD were set at 0.69 and 0.60, respectively [30]. AEs were assumed to reduce health utility, a concept known as disutility. This disutility associated with AEs was incorporated only in the first cycle of the model and was considered to occur once every three weeks.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\"\u003e\n \u003ch2\u003eScenario analysis\u003c/h2\u003e\n \u003cp\u003eGiven the high uncertainty about the model assumptions and the sources of the parameters in this research, scenario analyses were performed. For the US, without prior data on the price of tislelizumab, a price equivalent to that in Hong Kong (\u003cspan\u003e$\u003c/span\u003e1,277.14 per 100 mg) was used in the base-case analysis. The price varied between \u003cspan\u003e$\u003c/span\u003e0 and \u003cspan\u003e$\u003c/span\u003e5,000 to examine the potential cost-effectiveness under the WTP threshold of \u003cspan\u003e$\u003c/span\u003e150,000.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003eSensitivity analysis\u003c/h2\u003e\n \u003cp\u003eOne-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were conducted to evaluate the inherent uncertainty of the model. In the OWSA, the parameter range was derived from the existing literature, defined by 95% CIs or a\u0026thinsp;\u0026plusmn;\u0026thinsp;20% variation from baseline values. For PSA, the model parameters were varied simultaneously across 10,000 Monte Carlo simulations to assess the probability that each intervention was cost-effective, considering different WTP thresholds for an additional QALY. These simulations modeled utility parameters using beta distributions, while cost variables used gamma distributions. The results of these analyses are shown in a scatter plot and a cost-effectiveness acceptability curve.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eBase-case analysis\u003c/h2\u003e \u003cp\u003eDuring a 10-year analysis horizon, base-case results indicated that the tislelizumab plus chemotherapy group accrued an additional 0.96 QALYs at an incremental cost of \u003cspan\u003e$\u003c/span\u003e25,314.16. The chemotherapy-only group gained 0.69 QALYs with associated costs of \u003cspan\u003e$\u003c/span\u003e16,961.98. Comparative analysis showed a mean incremental effect of 0.27 QALYs at an additional cost of \u003cspan\u003e$\u003c/span\u003e8,352.18 for the tislelizumab group. This resulted in an ICER of \u003cspan\u003e$\u003c/span\u003e31,136.52 per QALY for tislelizumab plus chemotherapy compared to chemotherapy alone (\u003cb\u003eSupplemental Table\u0026nbsp;2\u003c/b\u003e). When evaluated against China\u0026rsquo;s WTP threshold of \u003cspan\u003e$\u003c/span\u003e38,042.49 per QALY, tislelizumab plus chemotherapy was more cost-effective than chemotherapy alone. The INHB was 0.05 QALYs, and the INMB was \u003cspan\u003e$\u003c/span\u003e1,852.49 (\u003cb\u003eSupplemental Table\u0026nbsp;2\u003c/b\u003e). In the US, the ICER for tislelizumab plus chemotherapy was \u003cspan\u003e$\u003c/span\u003e157,117.67 per QALY, exceeding the US WTP threshold of \u003cspan\u003e$\u003c/span\u003e150,000.00 per QALY (\u003cb\u003eSupplemental Table\u0026nbsp;2\u003c/b\u003e). Additionally, INHB was \u0026minus;\u0026thinsp;0.01 QALYs, and INMB was -\u003cspan\u003e$\u003c/span\u003e2,045.70, compared to chemotherapy alone at the \u003cspan\u003e$\u003c/span\u003e150,000.00 WTP threshold (\u003cb\u003eSupplemental Table\u0026nbsp;2\u003c/b\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePrice simulation\u003c/h2\u003e \u003cp\u003eThe results of the price simulation, shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, reveal that in the US since the price of tislelizumab ranged between \u003cspan\u003e$\u003c/span\u003e0 and \u003cspan\u003e$\u003c/span\u003e5,000.00 per 100 mg, the ICER increased accordingly. Tislelizumab was cost-effective when priced below \u003cspan\u003e$\u003c/span\u003e1,199.38 per 100 mg, adhering to the WTP threshold of \u003cspan\u003e$\u003c/span\u003e150,000.00.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analysis\u003c/h2\u003e \u003cp\u003e \u003cb\u003eSupplemental Fig.\u0026nbsp;1\u003c/b\u003e shows a tornado diagram from OWSA that analyzes the entire population. This diagram identifies the most influential factors on the base-case outcomes: the cost of tislelizumab, the utility value of PFS, and the cost of PET-CT scans. \u003cb\u003eSupplemental Fig.\u0026nbsp;2\u003c/b\u003e highlights that for US patients, ICER was mainly affected by the cost of tislelizumab, the proportion of patients in the tislelizumab plus chemotherapy group receiving subsequent systemic treatment, and the proportion in the placebo plus chemotherapy group receiving similar treatment. However, due to the minimal differences in health outcomes between the two treatment strategies between the two groups, various changes in parameter values significantly affected the study results.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSupplemental Figs.\u0026nbsp;3\u0026ndash;6\u003c/b\u003e, featuring acceptability curves and probabilistic scatter plots, offer a practical and visual representation of the cost-effectiveness landscape. These tools, which are crucial for decision-making, elucidate the probabilities that tislelizumab plus chemotherapy is considered cost-effective. PSA results indicate substantial probabilities, with rates of 86.49% in China and 44.07% in the US, corresponding to a WTP threshold of three times China\u0026rsquo;s GDP per capita (\u003cspan\u003e$\u003c/span\u003e38,042.49) and \u003cspan\u003e$\u003c/span\u003e150,000.00 in the US.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe RATIONALE-312 trial demonstrated that adding tislelizumab to chemotherapy significantly improved OS and other key efficacy outcomes in patients with ES-SCLC[14]. Although tislelizumab has been approved in China and the FDA has granted orphan drug status for SCLC, its high potential to reshape the global immunotherapy market for ES-SCLC is tempered by limited price information. This uncertainty poses a dilemma for physicians and patients in determining its cost-effectiveness, which requires a thorough economic analysis.\u003c/p\u003e \u003cp\u003eBased on the RATIONALE-312 trial, our economic analysis from the Chinese healthcare perspective shows that tislelizumab plus chemotherapy resulted in an ICER of \u003cspan\u003e$\u003c/span\u003e31,136.52 per QALY, below the WTP threshold of \u003cspan\u003e$\u003c/span\u003e38,042.49 per QALY. However, from the US perspective, the ICER reaches \u003cspan\u003e$\u003c/span\u003e157,117.67 per QALY, exceeding the US WTP threshold of \u003cspan\u003e$\u003c/span\u003e150,000.00. This analysis is further supported by the INHB and INMB findings, indicating INHBs of 0.05 and \u0026minus;\u0026thinsp;0.01 and INMBs of \u003cspan\u003e$\u003c/span\u003e1,852.49 and -\u003cspan\u003e$\u003c/span\u003e2,045.70, respectively, for the Chinese and US settings compared to chemotherapy alone.\u003c/p\u003e \u003cp\u003ePrevious studies have indicated that most immune checkpoint inhibitors combined with chemotherapy are not cost-effective as first-line therapy for patients with ES-SCLC [28, 29, 31\u0026ndash;35]. Common in these studies is the finding that the cost of PD-L1 antibodies significantly impacts outcomes. For example, in the US, the ICER for tislelizumab plus chemotherapy approximates the WTP threshold of \u003cspan\u003e$\u003c/span\u003e150,000.00 per QALY. The cost-effectiveness acceptability curve aligns with this, showing a 44.07% probability that this combination is cost-effective at a threshold of three times the GDP per capita per QALY. Sensitivity analyses confirm these results, with minor differences in health outcomes between the two strategies that significantly alter study results. In particular, we assumed that the price of tislelizumab was the same as in Hong Kong (\u003cspan\u003e$\u003c/span\u003e1,277.14 per 100 mg), which does not reflect its price in the United States. However, price simulations indicate that tislelizumab is favored when priced below \u003cspan\u003e$\u003c/span\u003e1,199.38 per 100 mg at the \u003cspan\u003e$\u003c/span\u003e150,000.00 WTP threshold.\u003c/p\u003e \u003cp\u003eThis study is the first to evaluate the cost-effectiveness of tislelizumab plus chemotherapy as first-line therapy for ES-SCLC from both the US and China perspectives. It offers information to US decision-makers on the pricing of tislelizumab should they consider supporting its entry into the US market. Additionally, due to the absence of quality of life (EQ-5D) and cost per QALY data in the RATIONALE-312 trial, we rely on utility values from the literature for PFS and PD. This approach, while necessary, introduces uncertainties in our modeled results. Importantly, unlike many studies that derive quality of life and health utility data from non-small cell lung cancer (NSCLC), our study uses data specifically from SCLC studies, enhancing the relevance and accuracy of our findings.\u003c/p\u003e \u003cp\u003eThis analysis has several limitations. First, clinical data were sourced from a phase 3 trial conducted in China, while cost-effectiveness analysis was performed from the perspective of US payers, which could introduce geographic bias. Second, the range of options for second-line treatments, such as chemotherapy, targeted therapy, immunotherapy, and radiation therapy, is complex and varied. Due to the absence of specific drug information in the corresponding clinical trials, assumptions were made about subsequent chemotherapy and the best supportive care. Third, this study did not account for the management costs and disutility associated with grade 1\u0026ndash;2 AEs. Given that the tislelizumab plus chemotherapy arm experienced a higher incidence of such AEs than the chemotherapy arm, this oversight might underestimate ICER. Despite these challenges, conducting a cost-effectiveness analysis based on data from the RATIONALE-312 study is still feasible and provides critical information for treatment decision-making.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis investigation reveals that combining tislelizumab with chemotherapy represents a cost-effective first-line treatment for patients with ES-SCLC within the Chinese healthcare system. However, this combination does not meet the same cost-effectiveness criteria in the US healthcare system. This analysis offers valuable guidance to decision-makers and healthcare professionals, providing robust evidence to support the expanded use of tislelizumab in clinical practices globally.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Drug clinical comprehensive evaluation project of Health Commission of Guangxi Zhuang Autonomous Region(Grant No. YPPJ014).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49. https://doi.org/10.3322/caac.21660.\u003c/li\u003e\n\u003cli\u003eOronsky B, Abrouk N, Caroen S et al. A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC). J Cancer. 2022;13(9):2945-53. https://doi.org/10.7150/jca.75622.\u003c/li\u003e\n\u003cli\u003eRudin CM, Brambilla E, Faivre-Finn C et al. Small-cell lung cancer. Nat Rev Dis Primers. 2021;7(1):3. https://doi.org/10.1038/s41572-020-00235-0.\u003c/li\u003e\n\u003cli\u003eSathiyapalan A, Febbraro M, Pond GR et al. Chemo-Immunotherapy in First Line Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Systematic Review and Meta-Analysis. Curr Oncol. 2022;29(12):9046-65. https://doi.org/10.3390/curroncol29120709.\u003c/li\u003e\n\u003cli\u003ePaz-Ares L, Dvorkin M, Chen Y et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-39. https://doi.org/10.1016/s0140-6736(19)32222-6.\u003c/li\u003e\n\u003cli\u003eRudin CM, Ismaila N, Hann CL et al. Treatment of Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline. J Clin Oncol. 2015;33(34):4106-11. https://doi.org/10.1200/jco.2015.63.7918.\u003c/li\u003e\n\u003cli\u003eRossi A, Di Maio M, Chiodini P et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol. 2012;30(14):1692-8. https://doi.org/10.1200/jco.2011.40.4905.\u003c/li\u003e\n\u003cli\u003eWang J, Zhou C, Yao W et al. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23(6):739-47. https://doi.org/10.1016/s1470-2045(22)00224-8.\u003c/li\u003e\n\u003cli\u003eHorn L, Mansfield AS, Szczęsna A et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018;379(23):2220-9. https://doi.org/10.1056/NEJMoa1809064.\u003c/li\u003e\n\u003cli\u003ePaz-Ares L, Chen Y, Reinmuth N et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7(2):100408. https://doi.org/10.1016/j.esmoop.2022.100408.\u003c/li\u003e\n\u003cli\u003eLiu SV, Reck M, Mansfield AS et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021;39(6):619-30. https://doi.org/10.1200/jco.20.01055.\u003c/li\u003e\n\u003cli\u003eCheng Y, Han L, Wu L et al. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial. Jama. 2022;328(12):1223-32. https://doi.org/10.1001/jama.2022.16464.\u003c/li\u003e\n\u003cli\u003eZhang T, Song X, Xu L et al. The binding of an anti-PD-1 antibody to Fc\u0026gamma;R\u0026Iota; has a profound impact on its biological functions. Cancer Immunol Immunother. 2018;67(7):1079-90. https://doi.org/10.1007/s00262-018-2160-x.\u003c/li\u003e\n\u003cli\u003eCheng Y, Fan Y, Zhao Y et al. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024. https://doi.org/10.1016/j.jtho.2024.03.008.\u003c/li\u003e\n\u003cli\u003eHusereau D, Drummond M, Augustovski F et al. Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) Statement: Updated Reporting Guidance for Health Economic Evaluations. Value Health. 2022;25(1):3-9. https://doi.org/10.1016/j.jval.2021.11.1351.\u003c/li\u003e\n\u003cli\u003eGanti AKP, Loo BW, Bassetti M et al. Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19(12):1441-64. https://doi.org/10.6004/jnccn.2021.0058.\u003c/li\u003e\n\u003cli\u003eGoulart B, Ramsey S. A trial-based assessment of the cost-utility of bevacizumab and chemotherapy versus chemotherapy alone for advanced non-small cell lung cancer. Value Health. 2011;14(6):836-45. https://doi.org/10.1016/j.jval.2011.04.004.\u003c/li\u003e\n\u003cli\u003eDieleman JL, Cao J, Chapin A et al. US Health Care Spending by Payer and Health Condition, 1996-2016. Jama. 2020;323(9):863-84. https://doi.org/10.1001/jama.2020.0734.\u003c/li\u003e\n\u003cli\u003eSu D, Wu B, Shi L. Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma. JAMA Netw Open. 2021;4(2):e210037. https://doi.org/10.1001/jamanetworkopen.2021.0037.\u003c/li\u003e\n\u003cli\u003eYue X, Li Y, Wu J et al. Current Development and Practice of Pharmacoeconomic Evaluation Guidelines for Universal Health Coverage in China. Value Health Reg Issues. 2021;24:1-5. https://doi.org/10.1016/j.vhri.2020.07.580.\u003c/li\u003e\n\u003cli\u003eMurray CJ, Evans DB, Acharya A et al. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ. 2000;9(3):235-51. https://doi.org/10.1002/(sici)1099-1050(200004)9:3\u0026lt;235::aid-hec502\u0026gt;3.0.co;2-o.\u003c/li\u003e\n\u003cli\u003eNeumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness--the curious resilience of the $50,000-per-QALY threshold. N Engl J Med. 2014;371(9):796-7. https://doi.org/10.1056/NEJMp1405158.\u003c/li\u003e\n\u003cli\u003eGuyot P, Ades AE, Ouwens MJ et al. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2012;12:9. https://doi.org/10.1186/1471-2288-12-9.\u003c/li\u003e\n\u003cli\u003eZhu Y, Liu K, Qin Q et al. Serplulimab plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: A cost-effectiveness analysis. Front Immunol. 2022;13:1044678. https://doi.org/10.3389/fimmu.2022.1044678.\u003c/li\u003e\n\u003cli\u003eLiu L, Wang L, Chen L et al. Cost-effectiveness of sintilimab plus chemotherapy versus chemotherapy alone as first-line treatment of locally advanced or metastatic oesophageal squamous cell carcinoma. Front Immunol. 2023;14:1092385. https://doi.org/10.3389/fimmu.2023.1092385.\u003c/li\u003e\n\u003cli\u003eCao X, Cai H, Li N et al. First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone for advanced esophageal cancer: a cost-effectiveness analysis. Ther Adv Med Oncol. 2022;14:17588359221122733. https://doi.org/10.1177/17588359221122733.\u003c/li\u003e\n\u003cli\u003eCenters for Medicare and Medicaid Services. Medicare Physician Fee Schedule Look-Up Tool (2021). Available at: https://www.cms.gov/medicare/physicianfee-schedule/search (Accessed 11January 2021)\u003c/li\u003e\n\u003cli\u003eShao T, Zhao M, Liang L et al. Serplulimab Plus Chemotherapy vs Chemotherapy for Treatment of US and Chinese Patients with Extensive-Stage Small-Cell Lung Cancer: A Cost-Effectiveness Analysis to Inform Drug Pricing. BioDrugs. 2023;37(3):421-32. https://doi.org/10.1007/s40259-023-00586-6.\u003c/li\u003e\n\u003cli\u003eLiu Q, Luo X, Yi L et al. First-Line Chemo-Immunotherapy for Extensive-Stage Small-Cell Lung Cancer: A United States-Based Cost-Effectiveness Analysis. Front Oncol. 2021;11:699781. https://doi.org/10.3389/fonc.2021.699781.\u003c/li\u003e\n\u003cli\u003eVedadi A, Shakik S, Brown MC et al. The impact of symptoms and comorbidity on health utility scores and health-related quality of life in small cell lung cancer using real world data. Qual Life Res. 2021;30(2):445-54. https://doi.org/10.1007/s11136-020-02615-1.\u003c/li\u003e\n\u003cli\u003eLong Y, Xu Y, Liao L et al. Cost-effectiveness analysis of serplulimab combined with chemotherapy in the treatment of extensive-stage small-cell lung cancer from the perspective of the healthcare system in China. BMJ Open. 2023;13(8):e072106. https://doi.org/10.1136/bmjopen-2023-072106.\u003c/li\u003e\n\u003cli\u003eZhou K, Zhou J, Huang J et al. Cost-effectiveness analysis of atezolizumab plus chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer. Lung Cancer. 2019;130:1-4. https://doi.org/10.1016/j.lungcan.2019.01.019.\u003c/li\u003e\n\u003cli\u003eXiang G, Jiang T, Gan L et al. Cost-effectiveness of serplulimab as first-line therapy for extensive-stage small cell lung cancer in China. Front Immunol. 2023;14:1223020. https://doi.org/10.3389/fimmu.2023.1223020.\u003c/li\u003e\n\u003cli\u003eWang Y, Rui M, Yang L et al. Economic Evaluation of First-Line Atezolizumab for Extensive-Stage Small-Cell Lung Cancer in the US. Front Public Health. 2021;9:650392. https://doi.org/10.3389/fpubh.2021.650392.\u003c/li\u003e\n\u003cli\u003eDing D, Hu H, Li S et al. Cost-Effectiveness Analysis of Durvalumab Plus Chemotherapy in the First-Line Treatment of Extensive-Stage Small Cell Lung Cancer. J Natl Compr Canc Netw. 2021;19(10):1141-7. https://doi.org/10.6004/jnccn.2020.7796.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-pharmacy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcp","sideBox":"Learn more about [International Journal of Clinical Pharmacy](https://www.springer.com/journal/11096)","snPcode":"11096","submissionUrl":"https://submission.nature.com/new-submission/11096/3","title":"International Journal of Clinical Pharmacy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Cost-effectiveness, extensive-stage small-cell lung cancer, tislelizumab, chemotherapy, Markov mode","lastPublishedDoi":"10.21203/rs.3.rs-4451605/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4451605/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTislelizumab combined with chemotherapy has shown significant clinical benefits in improving overall survival compared to chemotherapy alone for patients with extensive-stage small-cell lung cancer (ES-SCLC).\u003c/p\u003e\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eThis study aimed to evaluate its cost-effectiveness for both US and Chinese ES-SCLC patient populations.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eWe conducted an economic evaluation using a Markov state-transition model, reflecting the perspectives of US and Chinese healthcare payers. Baseline patient characteristics and essential clinical data were obtained from the RATIONALE-312 trial. The costs and utilities were derived from open-access databases and published literature. The primary outcomes measured included quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Uncertainties in the model were addressed by probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWSA).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn the base-case analysis, the addition of tislelizumab to chemotherapy provided an incremental gain of 0.27 QALYs at an additional cost of \u003cspan\u003e$\u003c/span\u003e8,352.18, resulting in an ICER of \u003cspan\u003e$\u003c/span\u003e31,136.52 per QALY. Although below the willingness-to-pay (WTP) threshold of China of \u003cspan\u003e$\u003c/span\u003e38,042.49 per QALY, the cost-effectiveness was marginal, with an INHB of 0.05 QALYs and an INMB of \u003cspan\u003e$\u003c/span\u003e1,852.49. In the US, despite a slightly higher effectiveness gain of 0.29 QALYs, the increased cost of \u003cspan\u003e$\u003c/span\u003e45,157.35 resulted in an unfavorable ICER of \u003cspan\u003e$\u003c/span\u003e157,117.67 per QALY, exceeding the US WTP threshold of \u003cspan\u003e$\u003c/span\u003e150,000.00. PSA showed probabilities of cost-effectiveness of tislelizumab plus chemotherapy at 92.52% in China and 44.07% in the US.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eTislelizumab with chemotherapy may be a cost-effective first-line treatment option for ES-SCLC in China but not the US, highlighting significant geographical disparities in healthcare economics.\u003c/p\u003e","manuscriptTitle":"Comparative cost-effectiveness of tislelizumab plus chemotherapy versus standard chemotherapy in first-line treatment for extensive-stage small cell lung cancer: perspectives from the U.S. and Chinese healthcare systems","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-11 18:25:59","doi":"10.21203/rs.3.rs-4451605/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revisions","date":"2024-06-12T07:35:15+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-05-25T15:01:49+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-25T13:05:04+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"International Journal of Clinical Pharmacy","date":"2024-05-22T05:23:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-21T13:21:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Pharmacy","date":"2024-05-20T22:09:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-pharmacy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijcp","sideBox":"Learn more about [International Journal of Clinical Pharmacy](https://www.springer.com/journal/11096)","snPcode":"11096","submissionUrl":"https://submission.nature.com/new-submission/11096/3","title":"International Journal of Clinical Pharmacy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"02155e6c-6111-4889-9e84-65fd9aae9ca8","owner":[],"postedDate":"June 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-16T16:08:14+00:00","versionOfRecord":{"articleIdentity":"rs-4451605","link":"https://doi.org/10.1007/s11096-024-01802-1","journal":{"identity":"international-journal-of-clinical-pharmacy","isVorOnly":false,"title":"International Journal of Clinical Pharmacy"},"publishedOn":"2024-09-14 15:57:41","publishedOnDateReadable":"September 14th, 2024"},"versionCreatedAt":"2024-06-11 18:25:59","video":"","vorDoi":"10.1007/s11096-024-01802-1","vorDoiUrl":"https://doi.org/10.1007/s11096-024-01802-1","workflowStages":[]},"version":"v1","identity":"rs-4451605","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4451605","identity":"rs-4451605","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}