Benefits of PARP inhibitor rechallenge in patients with platinum-sensitive recurrent ovarian cancer previously treated with a PARP inhibitor: A Multicenter Retrospective Study

Benefits of PARP inhibitor rechallenge in patients with platinum-sensitive recurrent ovarian cancer previously treated with a PARP inhibitor: A Multicenter Retrospective Study | 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 Benefits of PARP inhibitor rechallenge in patients with platinum-sensitive recurrent ovarian cancer previously treated with a PARP inhibitor: A Multicenter Retrospective Study Ami Jo, Tadahiro Shoji, Ayaka Kitamura, Miku Musashi, Shunsuke Tatsuki, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8617978/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background : Although poly(ADP-ribose) polymerase (PARP) inhibitor rechallenge has been explored for platinum-sensitive recurrent ovarian cancer, data in Japanese patients remain scarce. This retrospective study evaluated the safety and efficacy of PARP inhibitor rechallenge in this population. Patients and Methods : Twenty-eight Japanese patients with ovarian cancer who experienced platinum-sensitive recurrence during or after PARP inhibitor therapy and subsequently responded to platinum-based chemotherapy were included. Olaparib and niraparib were administered as PARP inhibitor rechallenge in 19 and 9 patients, respectively. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS) and adverse events (AEs). Results : The median follow-up period was 19 months (range, 3–47). Median PFS and OS in the overall population were 6 months (95% CI, 3–8) and 32 months (95% CI, 28–not reached), respectively. The median PFS for patients who had received two prior regimens was 6 months, compared with 5 months for those who had received three or more regimens, with no significant difference (p = 0.734). Grade ≥3 hematologic toxicities included neutropenia (n = 4), anemia (n = 7), and thrombocytopenia (n = 2). Non-hematologic toxicities included interstitial pneumonia, hypertension, and proteinuria, with one case each. No treatment-related deaths occurred. Conclusion s: PARP inhibitor rechallenge in Japanese patients with platinum-sensitive recurrent ovarian cancer demonstrated a manageable safety profile but limited efficacy. Larger, prospective studies incorporating molecular stratification are required to better define the clinical role of PARP inhibitor rechallenge. Ovarian cancer platinum-sensitive recurrence maintenance therapy PARP inhibitor rechallenge therapy Figures Figure 1 Figure 2 1. Introduction Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States, with approximately 324,000 new cases and 207,000 deaths reported worldwide in 2022 [ 1 ]. In Japan, more than 13,000 women are diagnosed annually, and approximately 5,000 die from the disease [ 2 , 3 ]. Standard treatment for ovarian cancer consists of maximal cytoreductive surgery and platinum-based chemotherapy [ 4 , 5 ]. However, many patients are diagnosed at an advanced stage, experience recurrence after primary treatment, and have limited progression-free survival (PFS). Consequently, 5-year survival rates remain poor, at approximately 40% for stage III and 20% for stage IV disease [ 6 , 7 ]. These limitations underscore the need for improved therapeutic strategies. Since the approval of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in 2014, the treatment landscape of ovarian cancer has changed substantially [ 6 ]. PARP inhibitor maintenance therapy is now standard for patients with platinum-sensitive recurrence who respond to platinum-based chemotherapy [ 8 – 12 ]. Olaparib is recommended after first-line chemotherapy for patients with BRCA1/2 mutations (BRCAm), while bevacizumab (BEV) plus olaparib is used for homologous recombination deficiency (HRD)-positive tumors [ 8 , 13 , 14 ]. Niraparib is widely used regardless of BRCA or HRD status [ 8 , 12 , 15 , 16 ]. However, the benefit of PARP inhibitor rechallenge after prior PARP inhibitor exposure remains unclear. The OReO/ENGOT-ov38 trial demonstrated a statistically significant but modest PFS benefit with olaparib rechallenge in patients with platinum-sensitive recurrence [ 17 ]. Thus, the clinical relevance of this strategy remains controversial. Real-world evidence for PARP inhibitor rechallenge is limited, particularly in Asian populations, and patient selection criteria have not been standardized. Moreover, BEV maintenance therapy is not feasible in all patients because of recurrence patterns or BEV-related toxicities such as hypertension, proteinuria, and thrombosis. Consequently, clinicians are often required to consider PARP inhibitor rechallenge despite limited supporting evidence. In this context, we retrospectively evaluated the safety and clinical efficacy of PARP inhibitor rechallenge in Japanese patients with platinum-sensitive recurrent ovarian cancer. 2. Patients and Methods This study was approved by the Ethics Committee of Iwate Medical University School of Medicine (approval number MH2023-091). 2.1 Patients Informed consent was obtained in the form of opt-out on the website. Those who rejected were excluded. Twenty-eight patients with ovarian cancer who experienced platinum-sensitive recurrence after treatment with PARP inhibitors at Iwate Medical University and Hachinohe Red Cross Hospital between April 1, 2020 and July 31, 2025 and subsequently responded to platinum-based chemotherapy and PARP inhibitor rechallenge were included. The primary endpoint was PFS, and the secondary endpoints were overall survival (OS) and AEs. 2.2 Selection criteria for PARP inhibitor rechallenge Olaparib or niraparib was administered as PARP inhibitor rechallenge, and the following criteria were used for drug selection: If the PARP inhibitor was previously administered for more than 6 months, the same drug was administered. If the PARP inhibitor was previously administered for less than 6 months, the other drug was administered. If the previous PARP inhibitor was administered at a reduced dose and the same drug was administered for rechallenge, the reduced dose was used initially. If the patient had grade 3 or higher AEs when receiving the previous PARP inhibitor, the other drug was considered. If the patient had grade 2 anemia or grade 1 thrombocytopenia at the start of the rechallenge, a change to the other drug was considered. On principle, olaparib was selected for rechallenge in patients with BRCA m. Rechallenge was considered only for patients who demonstrated an objective response to the most recent platinum-based chemotherapy, maintained adequate bone marrow, renal, and hepatic function, and had a performance status of 0–2. 2.3 PARP inhibitor rechallenge criteria Olaparib was initiated at 600 mg/day and niraparib at 200 mg/day if neutrophil counts were ≥1500/µL, hemoglobin levels were ≥ 10.0 g/dL, and platelet counts were 100000/µL. Dose reduction, withdrawal, and discontinuation criteria for olaparib and niraparib followed the protocols of the SOLO2 and NOVA trials, respectively [10,11]. Treatment was continued until progressive disease was diagnosed or until AEs which precluded continuation of treatment occurred. 2.4 Definitions For survival analyses, PFS was defined as the period from the initiation of PARP inhibitor rechallenge to disease progression or death from any cause in the absence of progression, whichever occurred first. OS was defined as the period from the initiation of PARP inhibitor rechallenge to the date of death from any cause. For living patients, the study was terminated on July 31, 2025. Initial PFS was defined as the period from the initial administration of the first PARP inhibitor to the date of recurrence. In addition, PFI was defined as the time from the last dose of platinum-based chemotherapy to the date of recurrence, whereas PARPi-FI was defined as the period from the final dose of the previous PARP inhibitor to the initiation of rechallenge therapy. Clinically, PFI reflects tumor platinum sensitivity, whereas PARPi-FI reflects the potential recovery of PARP inhibitor response following treatment interruption. Both intervals were analyzed owing to their possible relevance to rechallenge efficacy. 2.5 Diagnosis of recurrence and assessment of AEs Recurrence was evaluated and diagnosed using computed tomography (CT) according to RECIST ver. 1.1 [18]. The occurrence and severity of AEs, as well as that of treatment-related AEs were evaluated according to the Common Toxicity Criteria for Adverse Events ver. 5.0 JCOG Japanese version (CTCAE ver5.0-JCOG) [19]. 2.6 Statistical analysis The data cut-off date was July 31, 2025. The effect on survival was assessed by constructing Kaplan–Meier curves and applying a log-rank test. In addition, independent prognostic factors for PFS and OS were investigated using univariate and multivariate analyses of 4 factors: number of previous regimens, initial anti-tumor response before rechallenge, CA125 level before rechallenge. These covariates were selected based on clinical relevance and prior studies indicating their potential association with survival duration. All statistical analyses were performed using EZR ver. 1.68 (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R 2.9-1 (R Foundation for Statistical Computing, Vienna, Austria). More precisely, it is a modified version of R commander designed to incorporate statistical functions commonly used in biostatistics [20]. 3. Results 3.1 Patient characteristics Table 1 summarizes the background characteristics of the 28 patients enrolled in this study. Their median age was 65 years (range: 49–82). The PS was 0 in 25 (89.3%) and 1 in 3 (10.7%) patients. The histological type was high-grade serous carcinoma in 26 patients (92.9%), endometrioid carcinoma in 1 (3.6%) patient, and clear cell carcinoma in 1 (3.6%) patient. There were 3 patients each with BRCA m and HRD. Overall, 15 patients (53.6%) received two regimens of prior chemotherapy, 7 (25.0%) received three regimens, and 6 (21.4%) received four or more regimens. Twenty-four patients had previously received BEV therapy and four had not. Previously administered PARP inhibitors were olaparib in 20 patients (71.4%), niraparib in 7 (25.0%), and rucaparib in 1 patient (3.6%). Sixteen patients (57.1%) had been receiving these drugs for less than 12 months, and 12 (42.9%) for more than 12 months. The pre-PFS was <12 months in 15 patients (53.6%) and ≥12 months in 13 patients (46.4%). The platinum-free interval (PFI) was <12 months in 11 patients (39.3%) and ≥12 months in 17 patients (60.7%). The recurrence sites were intraperitoneal in 13 patients (46.4%), distant metastases in 9 patients (32.1%), and both intraperitoneal and distant metastases in 6 patients (21.4%). The anti-tumor response to platinum-based chemotherapy before the start of PARP inhibitor rechallenge was complete response in 6 patients (21.4%), partial response in 21 (75.0%), and no evidence of disease (NED) in 1 patient (3.6%). The PARP inhibitor-free interval was < 6 months in 9 patients (32.1%) and ˃ 6 months in 19 patients (67.8%). CA125 levels before the start of PARP inhibitor rechallenge were < 35 U/mL in 18 cases (64.3%) and ˃ 35 U/mL in 10 cases (35.7%). Platinum-based chemotherapy administered to the enrolled patients included TC (+ BEV) therapy in 15 patients (53.5%), TP (+ BEV) therapy in 4 patients (14.3%), DC + BEV therapy in 1 patient (3.6%), and PLDC (+ BEV) therapy in 8 patients (28.6%). Eighteen patients (64.3%) received chemotherapy with BEV, whereas 10 (35.7%) did not. 3.2 Treatment Fifteen patients who received BEV with their most recent platinum-based chemotherapy did not receive BEV maintenance therapy and received PARP inhibitor rechallenge. The primary reasons were BEV-related toxicities (hypertension in 5 patients and proteinuria in 2 patients) and clinical judgment that BEV maintenance was unnecessary given the long duration of the initial PARP inhibitor treatment (>18 months in 6 patients) or a long PARPi-FI (>18 months in 2 patients). Olaparib or niraparib were administered for PARP inhibitor rechallenge in 19 (67.9%) and 9 (32.1%) patients, respectively. Twelve of 28 patients underwent PARP inhibitor switching. The median treatment duration was limited, with 5 months for olaparib (range: 1–24) and 3 months for niraparib (range: 1–27), reflecting the modest efficacy of rechallenge therapy. To date, 3 patients have received treatment and 25 experienced the recurrence. Thirteen (46.4%) had platinum-resistant recurrence, of which 11 were switched to single-agent chemotherapy and 2 to palliative care. The remaining 12 (42.9%) had platinum-sensitive recurrence, of which 10 were switched to platinum-based chemotherapy, 1 to radiation therapy, and 1 to palliative care. 3.3 AEs Table 2 shows the AEs in the olaparib and niraparib groups. In the olaparib group, 8 (42.1%) patients underwent dose reduction and 5 (26.3%) experienced interrupted treatment. By contrast, in the niraparib group, 6 (66.7%) patients underwent dose reduction and 5 (55.6%) experienced interrupted treatment. Grade 3 or higher neutropenia was observed in 3 patients in the olaparib group and 1 patient in the niraparib group, anemia was observed in 5 patients in the olaparib group and 2 patients in the niraparib group, and thrombocytopenia was observed in 1 patient in each group. Hypertension was observed in 1 patient in the niraparib group, and proteinuria and interstitial pneumonia were observed in 1 patient each in the olaparib group. One patient discontinued treatment because of grade 3 interstitial pneumonia. In the olaparib group, two patients received a red blood cell transfusion, and one received a platelet transfusion. Similarly, in the niraparib group, one patient received a platelet transfusion. Although hematologic toxicities were common, they were generally manageable with dose modification or temporary treatment interruption, and no treatment-related deaths occurred. 3.4 Survival analysis The median PFS after starting initial PARP maintenance treatment in all patients was 11 months (95% CI, 8–16). The median follow-up period was 19 months (range: 3–47), and median PFS and OS in the overall population were 6 (95% CI, 3–8) and 32 [95% CI, 28–not reached (NR)] months, respectively (Figure 1a and 1b). The median PFS and OS for patients who had received two and three or more prior regimens were 6 (95% CI, 2–24) and 5 (95% CI, 3–8) months, and 29 [95% CI, 19–NR] and NR (95% CI, 18–NR) months, respectively, with no significant differences by previous number of regimens (Figure 2a and 2b). Univariate analyses of PFS and OS were performed for the previously mentioned 4 background factors. CA125 level was the only factor associated with prolonged PFS (Table 3a); however, no factors associated with prolonged OS were identified (Table 3b). Furthermore, in the multivariate analysis, the CA125 level emerged as an independent prognostic factor associated with PFS (Table 3c), whereas no prognostic factors for OS were identified (Table 3d). 4. Discussion More than 85% of the patients in the OReO/ENGOT-ov38 trial received more than three prior regimens [17]. Early-line rechallenge is generally defined as rechallenge after one or two prior platinum-based regimens, at a time when indicators of treatment sensitivity, such as an extended initial PFS, PFI, or PARPi-FI, suggest preserved PARP responsiveness. However, to date, no reports have evaluated the usefulness of early-line PARP inhibitor rechallenge in Japanese patients. Clinically, BEV is often used as maintenance therapy for platinum-sensitive recurrence, based on the OCEANS and MITO16B/MaNGO2 trials [21,22]. The ESGO-ESMO-ESP consensus conference recommendations endorse using a different agent for second-line maintenance therapy from that used initially. This means that if BEV was administered as the previous maintenance therapy, a PARP inhibitor should be used, and if a PARP inhibitor was administered as the previous maintenance therapy, BEV should be used [23]. However, not all patients with platinum-sensitive recurrence previously treated with PARP inhibitors who respond to platinum-based chemotherapy with BEV can be switched to BEV maintenance therapy because of the adverse events associated with this agent. Patients who are unable to receive BEV maintenance therapy may be selected for maintenance therapy with PARP inhibitor rechallenge. The present study retrospectively examined the benefits of rechallenge in these patients and in patients who received PARP inhibitor rechallenge after platinum-based chemotherapy without BEV. The median PFS in the overall population was 6 months, which was similar to the median PFS reported in the OReO/ENGOT-ov38 trial. In contrast, the PFS in the SOLO2 trial in platinum-sensitive recurrent ovarian cancer was 19.1 months [10], while that in the NOVA trial was 21.0 months in the germline BRCA m group and 9.3 months in the non- BRCA m group [11]. The PFS for PARP inhibitor rechallenge in our present study (6 months) was shorter than the initial treatment with a PARP inhibitor for platinum-sensitive recurrent ovarian cancer, and is thus not a satisfactory treatment option for use clinically. This finding was consistent with that of Morgan et al., who reported PARP inhibitor rechallenge in 10 patients in the MOLTO trial with a PFS of 4.4 months [24]. In the OReO/ENGOT-ov38 trial, 89.5% of patients underwent PARP inhibitor rechallenge in the late-line settings of three or more lines [17]. There are few reports of PARP inhibitor rechallenge in early-line settings. Therefore, in this study, subgroup analysis was performed by dividing patients into those who had received two and three or more previous chemotherapy regimens. The median PFS for two and three or more regimens were 6 and 5 months, respectively, with no significant difference ( p = 0.734). Similarly, the median OS were 29 months and NR, respectively ( p = 0.22). In the OReO/ENGOT-ov38 trial, the median PFS in the BRCAm cohort and non- BRCA m cohort was 4.3 and 5.3 months, respectively [17]. In our study, the median PFS for the previous two regimens was consistent with the PFS in the OReO/ENGOT-ov38 trial in the late-line setting. Rechallenge with PARP inhibitors in the early line for platinum-sensitive recurrence showed no potential for prolonging PFS and OS compared to that in the late lines. However, this study was based on a small number of patients, and further comparative studies involving larger patient cohorts are necessary. Herein, one patient experienced NED as anti-tumor response to platinum-based chemotherapy prior to PARP inhibitor rechallenge. The patient received platinum-based chemotherapy following secondary debulking surgery and has not experienced any recurrence to date. In principle, the treatment for platinum-resistant recurrence at our institution involves single-agent chemotherapy, although platinum rechallenge is aggressively used as a subsequent treatment for patients with PFI > 12 months. Tatsuki et al. reported that platinum rechallenge for platinum-resistant recurrent ovarian cancer with a PFI of ≥12 months significantly prolonged OS compared with that of patients with a PFI of ≤12 months [25]. Of the 28 patients enrolled in this study, 21 showed platinum-resistance recurrence, of whom 10 were rechallenged with platinum-based agents. The median OS for these 10 patients was 29 months (95% CI; 19–NR). The prolonged median OS of 32 months, despite a PFS of 6 months, may be due to the platinum rechallenge. In our institution, we also opt for platinum-based chemotherapy with BEV for platinum-sensitive recurrence during and after PARP inhibitor treatment to increase the response rates and the proportion of patients who switch to maintenance therapy. In our previous study, when such patients were treated with platinum-based chemotherapy using BEV, the response rate was 82.6% [26]. Of the 28 patients included in this study, 18 received platinum-based chemotherapy with BEV, whereas 10 were switched to PARP inhibitor rechallenge owing to BEV-related AEs. Platinum-resistant recurrence rates following initial PARP inhibitor maintenance have not been fully reported; however, estimates from PFS curves suggest approximately 20–25% with niraparib in PRIMA [15] and 5–10% in patients with BRCA m in SOLO1 [13]. However, in our study, platinum-resistant recurrence occurred in 46.4% of our cohort following PARP inhibitor rechallenge, consistent with a previously reported 45.5% rate in a retrospective study [27]. The present study findings suggest that PARP inhibitor rechallenge is more frequently associated with platinum-resistant recurrence than initial PARP inhibitor administration. This may be because PARP rechallenge induces new resistance or HRD is recovered owing to secondary mutations (reversion mutations) caused by sustained pressure from PARP inhibitors. Long-term administration or rechallenge with PARP inhibitors may induce BRCA reversion mutations, recover HRD, and lead to PARP inhibitor and platinum resistance [28-31]. This mechanism represents a major challenge in the management of patients undergoing prolonged PARP inhibitor therapy, as it can limit the efficacy of subsequent treatment lines. In our study, the relatively modest PFS following PARP inhibitor rechallenge (median 6 months) and high frequency of platinum-resistant recurrence (46.4%) may reflect the underlying molecular resistance driven by such reversion mechanisms. In terms of safety, we observed grade ≥3 hematologic and non-hematologic AEs. However, their frequency was similar to previous reports [10-17]. While one case of interstitial pneumonia led to definitive discontinuation, causality was unclear. Moreover, grade 3 hypertension and proteinuria likely reflected the residual effects of prior BEV treatment. Notably, most AEs were managed by dose reduction or treatment interruption, and no treatment-related deaths occurred. Overall, the safety profile of PARP inhibitor rechallenge aligned with expectations, and no new safety concerns emerged. Following univariate and multivariate analyses, a CA125 level < 35 U/ml immediately before PARP inhibitor rechallenge was deemed as a prognostic factor for PFS. Therefore, a CA125 level < 35 U/ml may serve as an indicator for future treatment selection in PARP inhibitor rechallenge. This study has several limitations. First, it was a retrospective study conducted at only two institutions, resulting in a limited sample size. Second, the criteria for selecting maintenance therapy (BEV vs. PARP inhibitor) following platinum-based chemotherapy with BEV were not standardized. Third, the relatively short follow-up period limited assessment of long-term safety, including myelodysplastic syndromes and acute myeloid leukemia. Fourth, BRCA and HRD testing were not routinely performed during the study period, which reflects the limitations of the current Japanese insurance system and may have influenced both treatment selection and outcome interpretation. Therefore, standardized, repeatable biomarker testing will be crucial for future rechallenge strategies. Fifth, the decision to administer PARP inhibitor rechallenge was made by each attending physician based on clinical judgment, potentially introducing selection bias. Finally, quality of life was not evaluated, despite its importance in managing recurrence. In conclusions, while PARP inhibitor rechallenge in Japanese patients with platinum-sensitive recurrent ovarian cancer demonstrated acceptable safety, it exhibited only limited clinical efficacy. These results highlight the need for further studies with larger cohorts, molecular stratification, and prospective validation to define the optimal use of PARP inhibitor rechallenge in this setting. This is the first to report the treatment outcome of PARP inhibitor rechallenge in Japanese patients with platinum-sensitive recurrent ovarian cancer. In the future, PARP inhibitor rechallenge in patients with only two previous regimens and the usefulness of switching PARP inhibitors for rechallenge may be evaluated. Declarations Conflict of interest None of the authors of this manuscript has any conflicts of interest to declare. Authors’ Contributions Jo A and Shoji T conceived the study, Musashi M, Tatsuki S, Jonai N, Chiba Y, Sato S, Takatori E, Kaido Y, Nagasawa T, and Kagabu M performed a literature search. Takahashi F performed analysis and interpretation of data. Takatori E prepared the original manuscript. Shoji T, Baba T, and Aida T performed drafting and revising the article. All Authors have read and agreed to the published version of the manuscript. Acknowledgements The authors would like to thank Editage (www. honya kucen ter. jp) for the English language review. References Bray F, Laversanne M, Sung H, et al. (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74:229–263. https://doi.org/10.3322/caac.21834 Cancer Registry and Statistics (JP) (2020) Cancer Information Service [Internet]. National Cancer Center, Tokyo. Available from: https://ganjoho.jp/reg_stat/statistics/index.html (accessed 1 Aug 2025). Yamagami W, Nagase S, Takahashi F, et al. (2017) Clinical statistics of gynecologic cancers in Japan. J Gynecol Oncol 28: e32. https://doi.org/10.3802/jgo.2017.28.e32 Ozols RF, Bundy BN, Greer BE, et al. (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol 21:3194–3200. https://doi.org/10.1200/JCO.2003.02.153 Sambasivan S (2022) Epithelial ovarian cancer: Review article. Cancer Treat Res Commun 33:100629. https://doi.org/10.1016/j.ctarc.2022.100629 Miaja MR, Coleman RL, Gonzalez-Martin A, et al. (2020) The forefront of ovarian cancer therapy: Update on PARP inhibitors. Ann Oncol 31:1148–1159. https://doi.org/10.1016/j.annonc.2020.07.004 Torre LA, Trabert B, DeSantis CE, et al. (2018) Ovarian cancer statistics, 2018. CA Cancer J Clin 68:284–296. https://doi.org/10.3322/caac.21456 National Comprehensive Cancer Network (NCCN) (2025) NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer, Version 3. Available from: https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf (accessed 15 Aug 2025). Ledermann J, Harter P, Gourley C, et al. (2012) Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366:1382–1392. https://doi.org/10.1056/NEJMoa1105535 Pujade-Lauraine E, Ledermann JA, Selle F, et al. (2017) Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): A double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 18:1274–1284. https://doi.org/10.1016/S1470-2045(17)30469-2 Mirza MR, Monk BJ, Herrstedt J, et al. (2016) Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 375:2154–2164. https://doi.org/10.1056/NEJMoa1611310 Wu XH, Zhu JQ, Yin RT, et al. (2021) Niraparib maintenance therapy using an individualized starting dose (NORA): A randomized, double-blind, placebo-controlled phase III trial. Ann Oncol 32:512–521. https://doi.org/10.1016/j.annonc.2020.12.018 Banerjee S, Moore KN, Colombo N, et al. (2021) Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCAm (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 22:1721–1731. https://doi.org/10.1016/S1470-2045(21)00531-3 Ray-Coquard I, Pautier P, Pignata S, et al. (2019) Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med 381:2416–2428. https://doi.org/10.1056/NEJMoa1911361 González-Martín A, Pothuri B, Vergote I, et al. (2019) Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 381:2391–2402. https://doi.org/10.1056/NEJMoa1910962 Li N, Zhu J, Yin R, et al. (2023) Treatment with niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer: A phase 3 randomized clinical trial. JAMA Oncol 9:1230–1237. https://doi.org/10.1001/jamaoncol.2023.1725 Pujade-Lauraine E, Selle F, Scambia G, et al. (2023) Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-Ov38): A phase IIIb trial. Ann Oncol 34:1152–1164. https://doi.org/10.1016/j.annonc.2023.06.007 Eisenhauer EA, Therasse P, Bogaerts J, et al. (2009) New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026 Japan Clinical Oncology Group (2025) Common Toxicity Criteria for Adverse Events version 5.0 Japanese Translation (CTCAE-JCOG). Available from: https://jcog.jp/assets/CTCAEv5J_20220901_v25_1.pdf (accessed 1 Aug 2025). Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458. https://doi.org/10.1038/bmt.2012.244 Aghajanian C, Blank SV, Goff BA, et al. (2012) OCEANS: A randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30:2039–2045. https://doi.org/10.1200/JCO.2012.42.0505 Pignata S, Lorusso D, Joly F, et al. (2021) Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: A randomised, phase 3 trial. Lancet Oncol 22:267–276. https://doi.org/10.1016/S1470-2045(20)30637-9 Ledermann JA, Matias-Guiu X, Amant F, et al. (2024) ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: Pathology and molecular biology and early, advanced and recurrent disease. Ann Oncol 35:248–266. https://doi.org/10.1016/j.annonc.2023.11.015 Morgan RD, Clamp AR, White DJ, et al. (2023) Multi-maintenance olaparib therapy in relapsed, germline BRCA1/2-mutant high-grade serous ovarian cancer (MOLTO): A phase II trial. Clin Cancer Res 29:2602–2611. https://doi.org/10.1158/1078-0432.CCR-22-3483 Tatsuki S, Shoji T, Abe M, et al. (2022) Efficacy and safety of platinum rechallenge in patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer: A multicenter retrospective study. Anticancer Res 42:4603–4610. https://doi.org/10.21873/anticanres.15961 Abe M, Shoji T, Chiba Y, et al. (2023) Efficacy and safety of platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance for recurrent ovarian, fallopian tube, and primary peritoneal cancer during PARP inhibitor therapy: A multicenter retrospective study. Anticancer Res 43:1265–1272. https://doi.org/10.21873/anticanres.16248 Yuan H, Li N, Wu L, et al. (2024) Subsequent management and outcomes after first-line PARP inhibitors progression in ovarian cancer patients. J Ovarian Res 17:70. https://doi.org/10.1186/s13048-024-01362-0 Dilmac S, Ozpolat B (2023) Mechanisms of PARP-inhibitor-resistance in BRCA-mutated breast cancer and new therapeutic approaches. Cancers 15:3642. https://doi.org/10.3390/cancers15143642 Collet L, Hanvic B, Turinetto M, et al. (2024) BRCA1/2 alterations and reversion mutations in the era of PARP inhibitors in high grade ovarian cancer: State of the art and forthcoming challenges. Front Oncol 14:1354427. https://doi.org/10.3389/fonc.2024.1354427 Zou Y, Zhang H, Chen P, et al. (2025) Clinical approaches to overcome PARP inhibitor resistance. Mol Cancer 24:156. https://doi.org/10.1186/s12943-025-02355-1 Walmsley CS, Jonsson P, Cheng ML, et al. (2024) Convergent evolution of BRCA2 reversion mutations under therapeutic pressure by PARP inhibition and platinum chemotherapy. NPJ Precis Oncol 8:34. https://doi.org/10.1038/s41698-024-00451-6 Tables Table 1. Patient characteristics (N=28) Age (year) median 65 range 49-82 PS 0 25 1 3 Stage I 3 II 1 III 17 IV 7 Histological type High-grade serous carcinoma 26 Endometrioid carcinoma 1 Clear cell carcinoma 1 t BRCA status 1 mutation 2 2 mutation 1 Non-mutation 6 Unexamined 19 Homologous recombination status Deficient 3 Proficient 3 Unexamined 22 Number of previous regimens 2 15 3 > 4 7 6 Prior BEV Yes 24 No 4 Previous PARP inhibitor Olaparib Niraparib Rucaparib 20 7 1 Initial PARP inhibitor administration period (months) Initial PFS (months) PFI (months) Recurrence site <12 ≧12 <12 ≧12 <12 ≧12 Intraperitoneal Distant metastasis Both 16 12 15 13 11 17 13 9 6 Anti-tumor response before rechallenge Platinum-based chemotherapy before rechallenge Combined BEV PARP inhibitor free interval (months) CA125 level before rechallenge (U/ml) CR PR NED TC（＋BEV） TP（＋BEV） DC＋BEV PLDC（＋BEV） With Without <6 ≧6 <35 ≧35 6 21 1 15 4 1 8 18 10 9 19 18 10 Table 2. Adverse events Olaparib (N=19) Niraparib (N=9) P value* (≧Grade3) G1 G2 G3 G4 G1 G2 G3 G4 Leucopenia 5 7 0 0 3 4 1 0 0.321 Neutropenia 4 5 3 0 3 3 1 0 1.0 Anemia 7 4 3 2 4 1 2 0 1.0 Thrombocytopenia 10 1 0 1 6 0 0 1 1.0 Febrile neutropenia 0 0 0 0 0 0 0 0 1.0 Nausea 9 2 0 0 2 1 0 0 1.0 Vomiting 0 1 0 0 0 0 0 0 1.0 Appetite loss 2 2 0 0 2 0 0 0 1.0 Dysgeusia 2 0 0 0 2 0 0 0 1.0 Fatigue 4 2 0 0 4 1 0 0 1.0 Sensory neuropathy 7 0 0 0 4 0 0 0 1.0 Mucositis 0 0 0 0 1 0 0 0 1.0 Constipation 4 0 0 0 1 1 0 0 1.0 Eczema 2 0 0 0 0 1 0 0 1.0 Interstitial pneumonia 0 0 1 0 0 0 0 0 0.321 Hypertension 7 0 0 0 1 1 1 0 0.321 Protein urea 4 1 1 0 4 2 0 0 0.321 G: grade; *Chi-squared Table 3a. Univariate analyses of PFS HR 95%CI P value Previous regimens (2/ > 3) 1.15 0.49 – 2.66 0.747 Initial PFS ( 12months) 0.65 0.28 - 1.54 0.326 Anti-tumor response before rechallenge (CR/PR) 2.52 0.74 – 8.54 0.137 CA125 value ( 30U/ml) 3.03 1.20 -7.64 0.019 Table 3b. Univariate analyses of OS HR 95%CI P value Previous regimens (2/ > 3) 0.37 0.07 – 1.92 0.238 Initial PFS ( 12months) 0.40 0.08 – 2.10 0.281 Anti-tumor response before rechallenge (CR/PR) 0.72 0.07 – 6.94 0.777 CA125 value ( 30U/ml) 1.27 0.24 - 6.62 0.779 Table 3c. Multivariate analyses of PFS HR 95%CI P value Previous regimens (2/ > 3) 0.90 0.34 – 2.37 0.834 Initial PFS ( 12months) 0.81 0.30 – 2.91 0.683 Anti-tumor response before rechallenge (CR/PR) 2.31 0.68 – 7.91 0.179 CA125 value ( 30U/ml) 2.74 1.02 - 7.39 0.045 Table 3d. Multivariate analyses of OS HR 95%CI P value Previous regimens (2/ > 3) 0.18 0.02 – 1.17 0.073 Initial PFS ( 12months) 0.15 0.02 - 1.23 0.078 Anti-tumor response before rechallenge (CR/PR) 0.41 0.04 – 4.57 0.471 CA125 value ( 30U/ml) 0.61 0.09 -4.12 0.619 Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 09 Feb, 2026 Reviewers invited by journal 08 Feb, 2026 Editor assigned by journal 21 Jan, 2026 First submitted to journal 16 Jan, 2026 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-8617978","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":587666773,"identity":"b7539d02-092e-4501-b1d9-94942b2aa9ff","order_by":0,"name":"Ami Jo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuElEQVRIiWNgGAWjYFACxgYGxn82IEbjAeK1MLClgRnEagEBtsNgijgt/NMOtz34wXPebm37YaAtNTbRBLVI3E5sN+yRuJ287UwiUMuxtNwGgnpuJ7ZJMxjcTjY7ANTC2HCYsBZ5sJaEc8lm5x8SqcUArOXAATuzG8TaYgjyS29DcoLZDaAtCcT4Re52+rMHPxvs7M3Opz988KHGhgjvAyMFRCSCVSYQoRyuxZ5IxaNgFIyCUTASAQBEJkiydQaEMQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0009-5064-6997","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":true,"prefix":"","firstName":"Ami","middleName":"","lastName":"Jo","suffix":""},{"id":587666774,"identity":"71b43bf2-3de1-4aca-9bcc-30aa66b4fd2d","order_by":1,"name":"Tadahiro Shoji","email":"","orcid":"https://orcid.org/0000-0002-9022-3333","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Tadahiro","middleName":"","lastName":"Shoji","suffix":""},{"id":587666775,"identity":"918780ff-86f6-403c-9c8a-8ff3c39d7bd6","order_by":2,"name":"Ayaka Kitamura","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Ayaka","middleName":"","lastName":"Kitamura","suffix":""},{"id":587666776,"identity":"c8f52a29-3510-4452-9fdc-bd647509883f","order_by":3,"name":"Miku Musashi","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Miku","middleName":"","lastName":"Musashi","suffix":""},{"id":587666777,"identity":"cbb30616-e52d-42d1-84dc-988fb223981d","order_by":4,"name":"Shunsuke Tatsuki","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Shunsuke","middleName":"","lastName":"Tatsuki","suffix":""},{"id":587666778,"identity":"75b2dfd7-fee9-4e07-ae68-0292fa3333f7","order_by":5,"name":"Nanako Jonai","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Nanako","middleName":"","lastName":"Jonai","suffix":""},{"id":587666779,"identity":"7fda5ae0-1d82-42c2-8a6c-5b1afb1b0f13","order_by":6,"name":"Yohei Chiba","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Yohei","middleName":"","lastName":"Chiba","suffix":""},{"id":587666780,"identity":"eaf763af-e809-48c8-8667-f8a2cdf39477","order_by":7,"name":"Sho Sato","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Sho","middleName":"","lastName":"Sato","suffix":""},{"id":587666781,"identity":"e0b4f47f-ba9f-459b-879e-64fec13c15f3","order_by":8,"name":"Eriko Takatori","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Eriko","middleName":"","lastName":"Takatori","suffix":""},{"id":587666782,"identity":"bcf1ff36-3a8b-4d0b-8c38-6874981d0229","order_by":9,"name":"Yoshitaka Kaido","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Yoshitaka","middleName":"","lastName":"Kaido","suffix":""},{"id":587666783,"identity":"83bf5e65-6734-4d7d-9527-c541e09c0d15","order_by":10,"name":"Takayuki Nagasawa","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Takayuki","middleName":"","lastName":"Nagasawa","suffix":""},{"id":587666784,"identity":"3f4c411b-6553-4fb4-98f2-0124e6de2cf4","order_by":11,"name":"Masahiro Kagabu","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Masahiro","middleName":"","lastName":"Kagabu","suffix":""},{"id":587666785,"identity":"536d7e4e-5c88-4961-840f-2cc3eca077f3","order_by":12,"name":"Fumiaki Takahashi","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Fumiaki","middleName":"","lastName":"Takahashi","suffix":""},{"id":587666786,"identity":"ca069ddd-14bc-4d9a-80f0-f78b0d141b51","order_by":13,"name":"Takeshi Aida","email":"","orcid":"","institution":"Hachinoe Red Cross Hospital: Hachinohe Sekijuji Byoin","correspondingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Aida","suffix":""},{"id":587666787,"identity":"c745fc30-7e6a-43b0-8a9a-f3688e177a13","order_by":14,"name":"Tsukasa Baba","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Tsukasa","middleName":"","lastName":"Baba","suffix":""}],"badges":[],"createdAt":"2026-01-16 11:20:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8617978/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8617978/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102593849,"identity":"d998f0b2-16cf-4da1-ae10-57f6a8290d4d","added_by":"auto","created_at":"2026-02-13 11:52:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":426736,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-free survival (PFS) and overall survival(OS) in the overall patients. Median PFS and OS in the overall population were 6 (95% CI, 3–8) (a) and 32 [95% CI, 28–not reached (NR)] months (b), respectively.\u003c/p\u003e","description":"","filename":"IJCOFig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-8617978/v1/9ecd4779a8a8210e453280b5.png"},{"id":102747879,"identity":"550318d0-d8e0-40e6-a16a-bf36e951f393","added_by":"auto","created_at":"2026-02-16 09:05:33","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":540837,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-free survival (PFS) and overall survival (OS) according to number of previous regimens.The median PFS and OS for patients who had received two and three or more prior regimens were 6 (95% CI, 2–24) and 5 (95% CI, 3–8) months(a), and 29 [95% CI, 19–NR] and NR (95% CI, 18–NR) months (b), respectively.\u003c/p\u003e","description":"","filename":"IJCOFig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-8617978/v1/b3b2eedfbd79394a874554a5.png"},{"id":102750714,"identity":"d44092e7-dda7-49b7-a9b7-88a5b169fc23","added_by":"auto","created_at":"2026-02-16 09:21:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1683034,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8617978/v1/1da33da5-08e0-4edc-bffb-49786795755d.pdf"}],"financialInterests":"","formattedTitle":"Benefits of PARP inhibitor rechallenge in patients with platinum-sensitive recurrent ovarian cancer previously treated with a PARP inhibitor: A Multicenter Retrospective Study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eOvarian cancer is the fifth leading cause of cancer-related deaths among women in the United States, with approximately 324,000 new cases and 207,000 deaths reported worldwide in 2022 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In Japan, more than 13,000 women are diagnosed annually, and approximately 5,000 die from the disease [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Standard treatment for ovarian cancer consists of maximal cytoreductive surgery and platinum-based chemotherapy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, many patients are diagnosed at an advanced stage, experience recurrence after primary treatment, and have limited progression-free survival (PFS). Consequently, 5-year survival rates remain poor, at approximately 40% for stage III and 20% for stage IV disease [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These limitations underscore the need for improved therapeutic strategies.\u003c/p\u003e \u003cp\u003eSince the approval of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in 2014, the treatment landscape of ovarian cancer has changed substantially [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. PARP inhibitor maintenance therapy is now standard for patients with platinum-sensitive recurrence who respond to platinum-based chemotherapy [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Olaparib is recommended after first-line chemotherapy for patients with BRCA1/2 mutations (BRCAm), while bevacizumab (BEV) plus olaparib is used for homologous recombination deficiency (HRD)-positive tumors [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Niraparib is widely used regardless of BRCA or HRD status [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, the benefit of PARP inhibitor rechallenge after prior PARP inhibitor exposure remains unclear. The OReO/ENGOT-ov38 trial demonstrated a statistically significant but modest PFS benefit with olaparib rechallenge in patients with platinum-sensitive recurrence [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Thus, the clinical relevance of this strategy remains controversial. Real-world evidence for PARP inhibitor rechallenge is limited, particularly in Asian populations, and patient selection criteria have not been standardized. Moreover, BEV maintenance therapy is not feasible in all patients because of recurrence patterns or BEV-related toxicities such as hypertension, proteinuria, and thrombosis. Consequently, clinicians are often required to consider PARP inhibitor rechallenge despite limited supporting evidence.\u003c/p\u003e \u003cp\u003eIn this context, we retrospectively evaluated the safety and clinical efficacy of PARP inhibitor rechallenge in Japanese patients with platinum-sensitive recurrent ovarian cancer.\u003c/p\u003e"},{"header":"2. Patients and Methods","content":"\u003cp\u003eThis study was approved by the Ethics Committee of Iwate Medical University School of Medicine (approval number MH2023-091).\u003c/p\u003e\n\u003cp\u003e2.1 Patients\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained in the form of opt-out on the website. Those who rejected were excluded. Twenty-eight patients with ovarian cancer who experienced platinum-sensitive recurrence after treatment with PARP inhibitors at Iwate Medical University and Hachinohe Red Cross Hospital between April 1, 2020 and July 31, 2025 and subsequently responded to platinum-based chemotherapy and PARP inhibitor rechallenge were included. The primary endpoint was PFS, and the secondary endpoints were overall survival (OS) and AEs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.2 Selection criteria for PARP inhibitor rechallenge\u003c/p\u003e\n\u003cp\u003eOlaparib or niraparib was administered as PARP inhibitor rechallenge, and the following criteria were used for drug selection:\u003c/p\u003e\n\u003cp\u003eIf the PARP inhibitor was previously administered for more than 6 months, the same drug was administered.\u003c/p\u003e\n\u003cp\u003eIf the PARP inhibitor was previously administered for less than 6 months, the other drug was administered.\u003c/p\u003e\n\u003cp\u003eIf the previous PARP inhibitor was administered at a reduced dose and the same drug was administered for rechallenge, the reduced dose was used initially.\u003c/p\u003e\n\u003cp\u003eIf the patient had grade 3 or higher AEs when receiving the previous PARP inhibitor, the other drug was considered.\u003c/p\u003e\n\u003cp\u003eIf the patient had grade 2 anemia or grade 1 thrombocytopenia at the start of the rechallenge, a change to the other drug was considered.\u003c/p\u003e\n\u003cp\u003eOn principle, olaparib was selected for rechallenge in patients with \u003cem\u003eBRCA\u003c/em\u003em.\u003c/p\u003e\n\u003cp\u003eRechallenge was considered only for patients who demonstrated an objective response to the most recent platinum-based chemotherapy, maintained adequate bone marrow, renal, and hepatic function, and had a performance status of 0–2.\u003c/p\u003e\n\u003cp\u003e2.3 PARP inhibitor rechallenge criteria\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOlaparib was initiated at 600 mg/day and niraparib at 200 mg/day if neutrophil counts were ≥1500/µL, hemoglobin levels were ≥ 10.0 g/dL, and platelet counts were 100000/µL. Dose reduction, withdrawal, and discontinuation criteria for olaparib and niraparib followed the protocols of the SOLO2 and NOVA trials, respectively [10,11]. Treatment was continued until progressive disease was diagnosed or until AEs which precluded continuation of treatment occurred.\u003c/p\u003e\n\u003cp\u003e2.4 Definitions\u003c/p\u003e\n\u003cp\u003eFor survival analyses, PFS was defined as the period from the initiation of PARP inhibitor rechallenge to disease progression or death from any cause in the absence of progression, whichever occurred first. OS was defined as the period from the initiation of PARP inhibitor rechallenge to the date of death from any cause. For living patients, the study was terminated on July 31, 2025. Initial PFS was defined as the period from the initial administration of the first PARP inhibitor to the date of recurrence. In addition, PFI was defined as the time from the last dose of platinum-based chemotherapy to the date of recurrence, whereas PARPi-FI was defined as the period from the final dose of the previous PARP inhibitor to the initiation of rechallenge therapy. Clinically, PFI reflects tumor platinum sensitivity, whereas PARPi-FI reflects the potential recovery of PARP inhibitor response following treatment interruption. Both intervals were analyzed owing to their possible relevance to rechallenge efficacy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.5 Diagnosis of recurrence and assessment of AEs\u003c/p\u003e\n\u003cp\u003eRecurrence was evaluated and diagnosed using computed tomography (CT) according to RECIST ver. 1.1 [18]. The occurrence and severity of AEs, as well as that of treatment-related AEs were evaluated according to the Common Toxicity Criteria for Adverse Events ver. 5.0 JCOG Japanese version (CTCAE ver5.0-JCOG) [19].\u003c/p\u003e\n\u003cp\u003e2.6 Statistical analysis\u003c/p\u003e\n\u003cp\u003eThe data cut-off date was July 31, 2025. The effect on survival was assessed by constructing Kaplan–Meier curves and applying a log-rank test. In addition, independent prognostic factors for PFS and OS were investigated using univariate and multivariate analyses of 4 factors: number of previous regimens, initial anti-tumor response before rechallenge, CA125 level before rechallenge. These covariates were selected based on clinical relevance and prior studies indicating their potential association with survival duration.\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using EZR ver. 1.68 (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R 2.9-1 (R Foundation for Statistical Computing, Vienna, Austria). More precisely, it is a modified version of R commander designed to incorporate statistical functions commonly used in biostatistics [20].\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e3.1 Patient characteristics\u003c/p\u003e\n\u003cp\u003eTable 1 summarizes the background characteristics of the 28 patients enrolled in this study. Their median age was 65 years (range: 49\u0026ndash;82). The PS was 0 in 25 (89.3%) and 1 in 3 (10.7%) patients. The histological type was high-grade serous carcinoma in 26 patients (92.9%), endometrioid carcinoma in 1 (3.6%) patient, and clear cell carcinoma in 1 (3.6%) patient. There were 3 patients each with \u003cem\u003eBRCA\u003c/em\u003em and HRD. Overall, 15 patients (53.6%) received two regimens of prior chemotherapy, 7 (25.0%) received three regimens, and 6 (21.4%) received four or more regimens. Twenty-four patients had previously received BEV therapy and four had not. Previously administered PARP inhibitors were olaparib in 20 patients (71.4%), niraparib in 7 (25.0%), and rucaparib in 1 patient (3.6%). Sixteen patients (57.1%) had been receiving these drugs for less than 12 months, and 12 (42.9%) for more than 12 months. The pre-PFS was \u0026lt;12 months in 15 patients (53.6%) and \u0026ge;12 months in 13 patients (46.4%). The platinum-free interval (PFI) was \u0026lt;12 months in 11 patients (39.3%) and \u0026ge;12 months in 17 patients (60.7%). The recurrence sites were intraperitoneal in 13 patients (46.4%), distant metastases in 9 patients (32.1%), and both intraperitoneal and distant metastases in 6 patients (21.4%). The anti-tumor response to platinum-based chemotherapy before the start of PARP inhibitor rechallenge was complete response in 6 patients (21.4%), partial response in 21 (75.0%), and no evidence of disease (NED) in 1 patient (3.6%). The PARP inhibitor-free interval was \u0026lt; 6 months in 9 patients (32.1%) and ˃ 6 months in 19 patients (67.8%). CA125 levels before the start of PARP inhibitor rechallenge were \u0026lt; 35 U/mL in 18 cases (64.3%) and ˃ 35 U/mL in 10 cases (35.7%). Platinum-based chemotherapy administered to the enrolled patients included TC (+ BEV) therapy in 15 patients (53.5%), TP (+ BEV) therapy in 4 patients (14.3%), DC + BEV therapy in 1 patient (3.6%), and PLDC (+ BEV) therapy in 8 patients (28.6%). Eighteen patients (64.3%) received chemotherapy with BEV, whereas 10 (35.7%) did not.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3.2 Treatment\u003c/p\u003e\n\u003cp\u003eFifteen patients who received BEV with their most recent platinum-based chemotherapy did not receive BEV maintenance therapy and received PARP inhibitor rechallenge. The primary reasons were BEV-related toxicities (hypertension in 5 patients and proteinuria in 2 patients) and clinical judgment that BEV maintenance was unnecessary given the long duration of the initial PARP inhibitor treatment (\u0026gt;18 months in 6 patients) or a long PARPi-FI (\u0026gt;18 months in 2 patients).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOlaparib or niraparib were administered for PARP inhibitor rechallenge in 19 (67.9%) and 9 (32.1%) patients, respectively. Twelve of 28 patients underwent PARP inhibitor switching. The median treatment duration was limited, with 5 months for olaparib (range: 1\u0026ndash;24) and 3 months for niraparib (range: 1\u0026ndash;27), reflecting the modest efficacy of rechallenge therapy. To date, 3 patients have received treatment and 25 experienced the recurrence. Thirteen (46.4%) had platinum-resistant recurrence, of which 11 were switched to single-agent chemotherapy and 2 to palliative care. The remaining 12 (42.9%) had platinum-sensitive recurrence, of which 10 were switched to platinum-based chemotherapy, 1 to radiation therapy, and 1 to palliative care.\u003c/p\u003e\n\u003cp\u003e3.3 AEs\u003c/p\u003e\n\u003cp\u003eTable 2 shows the AEs in the olaparib and niraparib groups. In the olaparib group, 8 (42.1%) patients underwent dose reduction and 5 (26.3%) experienced interrupted treatment. By contrast, in the niraparib group, 6 (66.7%) patients underwent dose reduction and 5 (55.6%) experienced interrupted treatment. Grade 3 or higher neutropenia was observed in 3 patients in the olaparib group and 1 patient in the niraparib group, anemia was observed in 5 patients in the olaparib group and 2 patients in the niraparib group, and thrombocytopenia was observed in 1 patient in each group. Hypertension was observed in 1 patient in the niraparib group, and proteinuria and interstitial pneumonia were observed in 1 patient each in the olaparib group.\u003c/p\u003e\n\u003cp\u003eOne patient discontinued treatment because of grade 3 interstitial pneumonia. In the olaparib group, two patients received a red blood cell transfusion, and one received a platelet transfusion. Similarly, in the niraparib group, one patient received a platelet transfusion. Although hematologic toxicities were common, they were generally manageable with dose modification or temporary treatment interruption, and no treatment-related deaths occurred.\u003c/p\u003e\n\u003cp\u003e3.4 Survival analysis\u003c/p\u003e\n\u003cp\u003eThe median PFS after starting initial PARP maintenance treatment in all patients was 11 months (95% CI, 8\u0026ndash;16). The median follow-up period was 19 months (range: 3\u0026ndash;47), and median PFS and OS in the overall population were 6 (95% CI, 3\u0026ndash;8) and 32 [95% CI, 28\u0026ndash;not reached (NR)] months, respectively (Figure 1a and 1b). The median PFS and OS for patients who had received two and three or more prior regimens were 6 (95% CI, 2\u0026ndash;24) and 5 (95% CI, 3\u0026ndash;8) months, and 29 [95% CI, 19\u0026ndash;NR] and NR (95% CI, 18\u0026ndash;NR) months, respectively, with no significant differences by previous number of regimens (Figure 2a and 2b).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnivariate analyses of PFS and OS were performed for the previously mentioned 4 background factors. CA125 level was the only factor associated with prolonged PFS (Table 3a); however, no factors associated with prolonged OS were identified (Table 3b). Furthermore, in the multivariate analysis, the CA125 level emerged as an independent prognostic factor associated with PFS (Table 3c), whereas no prognostic factors for OS were identified (Table 3d).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eMore than 85% of the patients in the OReO/ENGOT-ov38 trial received more than three prior regimens [17]. Early-line rechallenge is generally defined as rechallenge after one or two prior platinum-based regimens, at a time when indicators of treatment sensitivity, such as an extended initial PFS, PFI, or PARPi-FI, suggest preserved PARP responsiveness. However, to date, no reports have evaluated the usefulness of early-line PARP inhibitor rechallenge in Japanese patients.\u003c/p\u003e\n\u003cp\u003eClinically, BEV is often used as maintenance therapy for platinum-sensitive recurrence, based on the OCEANS and MITO16B/MaNGO2 trials [21,22]. The ESGO-ESMO-ESP consensus conference recommendations endorse using a different agent for second-line maintenance therapy from that used initially. This means that if BEV was administered as the previous maintenance therapy, a PARP inhibitor should be used, and if a PARP inhibitor was administered as the previous maintenance therapy, BEV should be used [23]. However, not all patients with platinum-sensitive recurrence previously treated with PARP inhibitors who respond to platinum-based chemotherapy with BEV can be switched to BEV maintenance therapy because of the adverse events associated with this agent. Patients who are unable to receive BEV maintenance therapy may be selected for maintenance therapy with PARP inhibitor rechallenge. The present study retrospectively examined the benefits of rechallenge in these patients and in patients who received PARP inhibitor rechallenge after platinum-based chemotherapy without BEV.\u003c/p\u003e\n\u003cp\u003eThe median PFS in the overall population was 6 months, which was similar to the median PFS reported in the OReO/ENGOT-ov38 trial. In contrast, the PFS in the SOLO2 trial in platinum-sensitive recurrent ovarian cancer was 19.1 months [10], while that in the NOVA trial was 21.0 months in the germline \u003cem\u003eBRCA\u003c/em\u003em group and 9.3 months in the non-\u003cem\u003eBRCA\u003c/em\u003em group [11]. The PFS for PARP inhibitor rechallenge in our present study (6 months) was shorter than the initial treatment with a PARP inhibitor for platinum-sensitive recurrent ovarian cancer, and is thus not a satisfactory treatment option for use clinically. This finding was consistent with that of Morgan et al., who reported PARP inhibitor rechallenge in 10 patients in the MOLTO trial with a PFS of 4.4 months [24].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the OReO/ENGOT-ov38 trial, 89.5% of patients underwent PARP inhibitor rechallenge in the late-line settings of three or more lines [17]. There are few reports of PARP inhibitor rechallenge in early-line settings. Therefore, in this study, subgroup analysis was performed by dividing patients into those who had received two and three or more previous chemotherapy regimens. The median PFS for two and three or more regimens were 6 and 5 months, respectively, with no significant difference (\u003cem\u003ep\u003c/em\u003e = 0.734). Similarly, the median OS were 29 months and NR, respectively (\u003cem\u003ep\u003c/em\u003e = 0.22). In the OReO/ENGOT-ov38 trial, the median PFS in the \u003cem\u003eBRCAm\u003c/em\u003e cohort and non-\u003cem\u003eBRCA\u003c/em\u003em cohort was 4.3 and 5.3 months, respectively [17]. In our study, the median PFS for the previous two regimens was consistent with the PFS in the OReO/ENGOT-ov38 trial in the late-line setting. Rechallenge with PARP inhibitors in the early line for platinum-sensitive recurrence showed no potential for prolonging PFS and OS compared to that in the late lines. However, this study was based on a small number of patients, and further comparative studies involving larger patient cohorts are necessary.\u003c/p\u003e\n\u003cp\u003eHerein, one patient experienced NED as anti-tumor response to platinum-based chemotherapy prior to PARP inhibitor rechallenge. The patient received platinum-based chemotherapy following secondary debulking surgery and has not experienced any recurrence to date. In principle, the treatment for platinum-resistant recurrence at our institution involves single-agent chemotherapy, although platinum rechallenge is aggressively used as a subsequent treatment for patients with PFI \u0026gt; 12 months. Tatsuki et al. reported that platinum rechallenge for platinum-resistant recurrent ovarian cancer with a PFI of \u0026ge;12 months significantly prolonged OS compared with that of patients with a PFI of \u0026le;12 months [25]. Of the 28 patients enrolled in this study, 21 showed platinum-resistance recurrence, of whom 10 were rechallenged with platinum-based agents. The median OS for these 10 patients was 29 months (95% CI; 19\u0026ndash;NR). The prolonged median OS of 32 months, despite a PFS of 6 months, may be due to the platinum rechallenge. In our institution, we also opt for platinum-based chemotherapy with BEV for platinum-sensitive recurrence during and after PARP inhibitor treatment to increase the response rates and the proportion of patients who switch to maintenance therapy. In our previous study, when such patients were treated with platinum-based chemotherapy using BEV, the response rate was 82.6% [26]. Of the 28 patients included in this study, 18 received platinum-based chemotherapy with BEV, whereas 10 were switched to PARP inhibitor rechallenge owing to BEV-related AEs.\u003c/p\u003e\n\u003cp\u003ePlatinum-resistant recurrence rates following initial PARP inhibitor maintenance have not been fully reported; however, estimates from PFS curves suggest approximately 20\u0026ndash;25% with niraparib in PRIMA [15] and 5\u0026ndash;10% in patients with \u003cem\u003eBRCA\u003c/em\u003em in SOLO1 [13]. However, in our study, platinum-resistant recurrence occurred in 46.4% of our cohort following PARP inhibitor rechallenge, consistent with a previously reported 45.5% rate in a retrospective study [27]. The present study findings suggest that PARP inhibitor rechallenge is more frequently associated with platinum-resistant recurrence than initial PARP inhibitor administration. This may be because PARP rechallenge induces new resistance or HRD is recovered owing to secondary mutations (reversion mutations) caused by sustained pressure from PARP inhibitors. Long-term administration or rechallenge with PARP inhibitors may induce BRCA reversion mutations, recover HRD, and lead to PARP inhibitor and platinum resistance [28-31]. This mechanism represents a major challenge in the management of patients undergoing prolonged PARP inhibitor therapy, as it can limit the efficacy of subsequent treatment lines. In our study, the relatively modest PFS following PARP inhibitor rechallenge (median 6 months) and high frequency of platinum-resistant recurrence (46.4%) may reflect the underlying molecular resistance driven by such reversion mechanisms.\u003c/p\u003e\n\u003cp\u003eIn terms of safety, we observed grade \u0026ge;3 hematologic and non-hematologic AEs. However, their frequency was similar to previous reports [10-17]. While one case of interstitial pneumonia led to definitive discontinuation, causality was unclear. Moreover, grade 3 hypertension and proteinuria likely reflected the residual effects of prior BEV treatment. Notably, most AEs were managed by dose reduction or treatment interruption, and no treatment-related deaths occurred. Overall, the safety profile of PARP inhibitor rechallenge aligned with expectations, and no new safety concerns emerged.\u003c/p\u003e\n\u003cp\u003eFollowing univariate and multivariate analyses, a CA125 level \u0026lt; 35 U/ml immediately before PARP inhibitor rechallenge was deemed as a prognostic factor for PFS. Therefore, a CA125 level \u0026lt; 35 U/ml may serve as an indicator for future treatment selection in PARP inhibitor rechallenge.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, it was a retrospective study conducted at only two institutions, resulting in a limited sample size. Second, the criteria for selecting maintenance therapy (BEV vs. PARP inhibitor) following platinum-based chemotherapy with BEV were not standardized. Third, the relatively short follow-up period limited assessment of long-term safety, including myelodysplastic syndromes and acute myeloid leukemia. Fourth, \u003cem\u003eBRCA\u003c/em\u003e and HRD testing were not routinely performed during the study period, which reflects the limitations of the current Japanese insurance system and may have influenced both treatment selection and outcome interpretation. Therefore, standardized, repeatable biomarker testing will be crucial for future rechallenge strategies. Fifth, the decision to administer PARP inhibitor rechallenge was made by each attending physician based on clinical judgment, potentially introducing selection bias. Finally, quality of life was not evaluated, despite its importance in managing recurrence.\u003c/p\u003e\n\u003cp\u003eIn conclusions, while PARP inhibitor rechallenge in Japanese patients with platinum-sensitive recurrent ovarian cancer demonstrated acceptable safety, it exhibited only limited clinical efficacy. These results highlight the need for further studies with larger cohorts, molecular stratification, and prospective validation to define the optimal use of PARP inhibitor rechallenge in this setting. This is the first to report the treatment outcome of PARP inhibitor rechallenge in Japanese patients with platinum-sensitive recurrent ovarian cancer. In the future, PARP inhibitor rechallenge in patients with only two previous regimens and the usefulness of switching PARP inhibitors for rechallenge may be evaluated.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflict of interest None of the authors of this manuscript has any conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJo A and Shoji T conceived the study, Musashi M, Tatsuki S, Jonai N, Chiba Y, Sato S, Takatori E, Kaido Y, Nagasawa T, and Kagabu M performed a literature search. Takahashi F performed analysis and interpretation of data. Takatori E prepared the original manuscript. Shoji T, Baba T, and Aida T performed drafting and revising the article. All Authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Editage (www. honya kucen ter. jp) for the English language review.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Laversanne M, Sung H, et al. (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74:229\u0026ndash;263. https://doi.org/10.3322/caac.21834\u003c/li\u003e\n\u003cli\u003eCancer Registry and Statistics (JP) (2020) Cancer Information Service [Internet]. National Cancer Center, Tokyo. Available from: https://ganjoho.jp/reg_stat/statistics/index.html (accessed 1 Aug 2025).\u003c/li\u003e\n\u003cli\u003eYamagami W, Nagase S, Takahashi F, et al. (2017) Clinical statistics of gynecologic cancers in Japan. J Gynecol Oncol 28: e32. https://doi.org/10.3802/jgo.2017.28.e32\u003c/li\u003e\n\u003cli\u003eOzols RF, Bundy BN, Greer BE, et al. (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol 21:3194\u0026ndash;3200. https://doi.org/10.1200/JCO.2003.02.153\u003c/li\u003e\n\u003cli\u003eSambasivan S (2022) Epithelial ovarian cancer: Review article. Cancer Treat Res Commun 33:100629. https://doi.org/10.1016/j.ctarc.2022.100629\u003c/li\u003e\n\u003cli\u003eMiaja MR, Coleman RL, Gonzalez-Martin A, et al. (2020) The forefront of ovarian cancer therapy: Update on PARP inhibitors. Ann Oncol 31:1148\u0026ndash;1159. https://doi.org/10.1016/j.annonc.2020.07.004\u003c/li\u003e\n\u003cli\u003eTorre LA, Trabert B, DeSantis CE, et al. (2018) Ovarian cancer statistics, 2018. CA Cancer J Clin 68:284\u0026ndash;296. https://doi.org/10.3322/caac.21456\u003c/li\u003e\n\u003cli\u003eNational Comprehensive Cancer Network (NCCN) (2025) NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer, Version 3. Available from: https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf (accessed 15 Aug 2025).\u003c/li\u003e\n\u003cli\u003eLedermann J, Harter P, Gourley C, et al. (2012) Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366:1382\u0026ndash;1392. https://doi.org/10.1056/NEJMoa1105535\u003c/li\u003e\n\u003cli\u003ePujade-Lauraine E, Ledermann JA, Selle F, et al. (2017) Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): A double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 18:1274\u0026ndash;1284. https://doi.org/10.1016/S1470-2045(17)30469-2\u003c/li\u003e\n\u003cli\u003eMirza MR, Monk BJ, Herrstedt J, et al. (2016) Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 375:2154\u0026ndash;2164. https://doi.org/10.1056/NEJMoa1611310\u003c/li\u003e\n\u003cli\u003eWu XH, Zhu JQ, Yin RT, et al. (2021) Niraparib maintenance therapy using an individualized starting dose (NORA): A randomized, double-blind, placebo-controlled phase III trial. Ann Oncol 32:512\u0026ndash;521. https://doi.org/10.1016/j.annonc.2020.12.018\u003c/li\u003e\n\u003cli\u003eBanerjee S, Moore KN, Colombo N, et al. (2021) Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCAm (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 22:1721\u0026ndash;1731. https://doi.org/10.1016/S1470-2045(21)00531-3\u003c/li\u003e\n\u003cli\u003eRay-Coquard I, Pautier P, Pignata S, et al. (2019) Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med 381:2416\u0026ndash;2428. https://doi.org/10.1056/NEJMoa1911361\u003c/li\u003e\n\u003cli\u003eGonz\u0026aacute;lez-Mart\u0026iacute;n A, Pothuri B, Vergote I, et al. (2019) Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 381:2391\u0026ndash;2402. https://doi.org/10.1056/NEJMoa1910962\u003c/li\u003e\n\u003cli\u003eLi N, Zhu J, Yin R, et al. (2023) Treatment with niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer: A phase 3 randomized clinical trial. JAMA Oncol 9:1230\u0026ndash;1237. https://doi.org/10.1001/jamaoncol.2023.1725\u003c/li\u003e\n\u003cli\u003ePujade-Lauraine E, Selle F, Scambia G, et al. (2023) Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-Ov38): A phase IIIb trial. Ann Oncol 34:1152\u0026ndash;1164. https://doi.org/10.1016/j.annonc.2023.06.007\u003c/li\u003e\n\u003cli\u003eEisenhauer EA, Therasse P, Bogaerts J, et al. (2009) New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228\u0026ndash;247. https://doi.org/10.1016/j.ejca.2008.10.026\u003c/li\u003e\n\u003cli\u003eJapan Clinical Oncology Group (2025) Common Toxicity Criteria for Adverse Events version 5.0 Japanese Translation (CTCAE-JCOG). Available from: https://jcog.jp/assets/CTCAEv5J_20220901_v25_1.pdf (accessed 1 Aug 2025).\u003c/li\u003e\n\u003cli\u003eKanda Y (2013) Investigation of the freely available easy-to-use software \u0026lsquo;EZR\u0026rsquo; for medical statistics. Bone Marrow Transplant 48:452\u0026ndash;458. https://doi.org/10.1038/bmt.2012.244\u003c/li\u003e\n\u003cli\u003eAghajanian C, Blank SV, Goff BA, et al. (2012) OCEANS: A randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30:2039\u0026ndash;2045. https://doi.org/10.1200/JCO.2012.42.0505\u003c/li\u003e\n\u003cli\u003ePignata S, Lorusso D, Joly F, et al. (2021) Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: A randomised, phase 3 trial. Lancet Oncol 22:267\u0026ndash;276. https://doi.org/10.1016/S1470-2045(20)30637-9\u003c/li\u003e\n\u003cli\u003eLedermann JA, Matias-Guiu X, Amant F, et al. (2024) ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: Pathology and molecular biology and early, advanced and recurrent disease. Ann Oncol 35:248\u0026ndash;266. https://doi.org/10.1016/j.annonc.2023.11.015\u003c/li\u003e\n\u003cli\u003eMorgan RD, Clamp AR, White DJ, et al. (2023) Multi-maintenance olaparib therapy in relapsed, germline BRCA1/2-mutant high-grade serous ovarian cancer (MOLTO): A phase II trial. Clin Cancer Res 29:2602\u0026ndash;2611. https://doi.org/10.1158/1078-0432.CCR-22-3483\u003c/li\u003e\n\u003cli\u003eTatsuki S, Shoji T, Abe M, et al. (2022) Efficacy and safety of platinum rechallenge in patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer: A multicenter retrospective study. Anticancer Res 42:4603\u0026ndash;4610. https://doi.org/10.21873/anticanres.15961\u003c/li\u003e\n\u003cli\u003eAbe M, Shoji T, Chiba Y, et al. (2023) Efficacy and safety of platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance for recurrent ovarian, fallopian tube, and primary peritoneal cancer during PARP inhibitor therapy: A multicenter retrospective study. Anticancer Res 43:1265\u0026ndash;1272. https://doi.org/10.21873/anticanres.16248\u003c/li\u003e\n\u003cli\u003eYuan H, Li N, Wu L, et al. (2024) Subsequent management and outcomes after first-line PARP inhibitors progression in ovarian cancer patients. J Ovarian Res 17:70. https://doi.org/10.1186/s13048-024-01362-0\u003c/li\u003e\n\u003cli\u003eDilmac S, Ozpolat B (2023) Mechanisms of PARP-inhibitor-resistance in BRCA-mutated breast cancer and new therapeutic approaches. Cancers 15:3642. https://doi.org/10.3390/cancers15143642\u003c/li\u003e\n\u003cli\u003eCollet L, Hanvic B, Turinetto M, et al. (2024) BRCA1/2 alterations and reversion mutations in the era of PARP inhibitors in high grade ovarian cancer: State of the art and forthcoming challenges. Front Oncol 14:1354427. https://doi.org/10.3389/fonc.2024.1354427\u003c/li\u003e\n\u003cli\u003eZou Y, Zhang H, Chen P, et al. (2025) Clinical approaches to overcome PARP inhibitor resistance. Mol Cancer 24:156. https://doi.org/10.1186/s12943-025-02355-1\u003c/li\u003e\n\u003cli\u003eWalmsley CS, Jonsson P, Cheng ML, et al. (2024) Convergent evolution of BRCA2 reversion mutations under therapeutic pressure by PARP inhibition and platinum chemotherapy. NPJ Precis Oncol 8:34. https://doi.org/10.1038/s41698-024-00451-6\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Patient characteristics (N=28)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"511\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eAge\u0026nbsp;(year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003emedian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003erange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e49-82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003ePS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eStage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eHistological type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eHigh-grade serous carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEndometrioid carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eClear cell carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003et\u003cem\u003eBRCA\u003c/em\u003e status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e1 mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e2 mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eNon-mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eUnexamined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eHomologous recombination status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eDeficient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eProficient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eUnexamined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eNumber of previous regimens\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e\u003cu\u003e\u0026gt;\u003c/u\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003ePrior BEV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003ePrevious PARP inhibitor\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eOlaparib\u003c/p\u003e\n \u003cp\u003eNiraparib\u003c/p\u003e\n \u003cp\u003eRucaparib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eInitial PARP inhibitor administration\u003c/p\u003e\n \u003cp\u003eperiod (months)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eInitial PFS (months)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePFI (months)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRecurrence site\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e\u0026lt;12\u003c/p\u003e\n \u003cp\u003e≧12\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;12\u003c/p\u003e\n \u003cp\u003e≧12\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;12\u003c/p\u003e\n \u003cp\u003e≧12\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eIntraperitoneal\u003c/p\u003e\n \u003cp\u003eDistant metastasis\u003c/p\u003e\n \u003cp\u003eBoth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003eAnti-tumor response before rechallenge\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePlatinum-based chemotherapy before rechallenge\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCombined BEV\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePARP inhibitor free interval (months)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCA125 level before rechallenge (U/ml)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003cp\u003eNED\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eTC（＋BEV）\u003c/p\u003e\n \u003cp\u003eTP（＋BEV）\u003c/p\u003e\n \u003cp\u003eDC＋BEV\u003c/p\u003e\n \u003cp\u003ePLDC（＋BEV）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;6\u003c/p\u003e\n \u003cp\u003e≧6\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;35\u003c/p\u003e\n \u003cp\u003e≧35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2.\u003c/strong\u003e Adverse events\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"528\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eOlaparib (N=19)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eNiraparib (N=9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eP value*\u003c/p\u003e\n \u003cp\u003e(≧Grade3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eG1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eG4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eG1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eG4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eLeucopenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.321\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eNeutropenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eThrombocytopenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eFebrile neutropenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eNausea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eVomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eAppetite loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eDysgeusia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eSensory neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eMucositis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eConstipation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eEczema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eInterstitial pneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.321\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.321\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eProtein urea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.321\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eG: grade; *Chi-squared\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3a.\u003c/strong\u003e Univariate\u0026nbsp;analyses of PFS\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"465\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePrevious regimens (2/\u003cu\u003e\u0026gt;\u003c/u\u003e3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.49 \u0026ndash; 2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.747\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eInitial\u0026nbsp;PFS (\u0026lt;12months/\u003cu\u003e\u0026gt;\u003c/u\u003e12months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.28 - 1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.326\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eAnti-tumor response\u0026nbsp;before rechallenge\u0026nbsp;(CR/PR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e2.52 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.74 \u0026ndash; 8.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.137\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eCA125 value (\u0026lt;30U/ml/\u003cu\u003e\u0026gt;\u003c/u\u003e30U/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e3.03 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.20 -7.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3b.\u003c/strong\u003e Univariate analyses of OS\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"465\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePrevious regimens (2/\u003cu\u003e\u0026gt;\u003c/u\u003e3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.37 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.07 \u0026ndash; 1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.238\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eInitial\u0026nbsp;PFS (\u0026lt;12months/\u003cu\u003e\u0026gt;\u003c/u\u003e12months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.08 \u0026ndash; 2.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.281\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eAnti-tumor response\u0026nbsp;before rechallenge\u0026nbsp;(CR/PR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.72 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.07 \u0026ndash; 6.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.777\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eCA125 value (\u0026lt;30U/ml/\u003cu\u003e\u0026gt;\u003c/u\u003e30U/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e1.27 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.24 - 6.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.779\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3c.\u003c/strong\u003e Multivariate analyses of PFS\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"465\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePrevious regimens (2/\u003cu\u003e\u0026gt;\u003c/u\u003e3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.90 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.34 \u0026ndash; 2.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.834\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eInitial\u0026nbsp;PFS (\u0026lt;12months/\u003cu\u003e\u0026gt;\u003c/u\u003e12months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.81 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.30 \u0026ndash; 2.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.683\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eAnti-tumor response\u0026nbsp;before rechallenge\u0026nbsp;(CR/PR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e2.31 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.68 \u0026ndash; 7.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.179\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eCA125 value (\u0026lt;30U/ml/\u003cu\u003e\u0026gt;\u003c/u\u003e30U/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e2.74 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.02 - 7.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3d.\u003c/strong\u003e Multivariate analyses of OS\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"465\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e95%CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003ePrevious regimens (2/\u003cu\u003e\u0026gt;\u003c/u\u003e3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.18\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.02 \u0026ndash; 1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eInitial\u0026nbsp;PFS (\u0026lt;12months/\u003cu\u003e\u0026gt;\u003c/u\u003e12months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.02 - 1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eAnti-tumor response\u0026nbsp;before rechallenge\u0026nbsp;(CR/PR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.41 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.04 \u0026ndash; 4.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003eCA125 value (\u0026lt;30U/ml/\u003cu\u003e\u0026gt;\u003c/u\u003e30U/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.61 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.09 -4.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.619\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\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-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Ovarian cancer, platinum-sensitive recurrence, maintenance therapy, PARP inhibitor rechallenge therapy","lastPublishedDoi":"10.21203/rs.3.rs-8617978/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8617978/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Although poly(ADP-ribose) polymerase (PARP) inhibitor rechallenge has been explored for platinum-sensitive recurrent ovarian cancer, data in Japanese patients remain scarce. This retrospective study evaluated the safety and efficacy of PARP inhibitor rechallenge in this population.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and Methods\u003c/strong\u003e: Twenty-eight Japanese patients with ovarian cancer who experienced platinum-sensitive recurrence during or after PARP inhibitor therapy and subsequently responded to platinum-based chemotherapy were included. Olaparib and niraparib were administered as PARP inhibitor rechallenge in 19 and 9 patients, respectively. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS) and adverse events (AEs).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The median follow-up period was 19 months (range, 3–47). Median PFS and OS in the overall population were 6 months (95% CI, 3–8) and 32 months (95% CI, 28–not reached), respectively. The median PFS for patients who had received two prior regimens was 6 months, compared with 5 months for those who had received three or more regimens, with no significant difference (p = 0.734). Grade ≥3 hematologic toxicities included neutropenia (n = 4), anemia (n = 7), and thrombocytopenia (n = 2). Non-hematologic toxicities included interstitial pneumonia, hypertension, and proteinuria, with one case each. No treatment-related deaths occurred.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003es: PARP inhibitor rechallenge in Japanese patients with platinum-sensitive recurrent ovarian cancer demonstrated a manageable safety profile but limited efficacy. Larger, prospective studies incorporating molecular stratification are required to better define the clinical role of PARP inhibitor rechallenge.\u003c/p\u003e","manuscriptTitle":"Benefits of PARP inhibitor rechallenge in patients with platinum-sensitive recurrent ovarian cancer previously treated with a PARP inhibitor: A Multicenter Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-13 11:52:20","doi":"10.21203/rs.3.rs-8617978/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-02-09T06:47:15+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-08T09:40:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-21T08:28:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Oncology","date":"2026-01-16T05:58:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3090a359-22f9-4a26-a6f1-82798aee69f1","owner":[],"postedDate":"February 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-28T14:36:39+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-13 11:52:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8617978","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8617978","identity":"rs-8617978","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}