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Objective: In patients with platinum-sensitive relapsed ovarian cancer (PSROC) harboring pathogenic/likely pathogenic variants (PV) in BRCA1 and BRCA2 genes, olaparib maintenance monotherapy (OMT) is a viable option. Our study aimed to evaluate the impact of different BRCA1/2 PV in survival outcomes and safety of OMT in BRCA1/2-mutated PSROC patients, focusing on the type and location of PV., Methods: We assessed the outcomes of 100 BRCA1/2-mutated PSROC patients treated at our institute, analyzing progression-free survival (PFS) and overall survival (OS). Germline and tumor BRCA1/2 genotyping was conducted using Illumina's next-generation sequencing (NGS)., Results: PFS and OS were significantly shorter in PSROC patients with PV in BRCA1 compared to those with PV in BRCA2 (PFS:14.0 vs. 38.8 months, p = 0.007, OS: 21.8 vs. 62.0 months, p = 0.011). Notably, there was a significant difference in PFS based on the intragenic location of BRCA1 PV, with shorter PFS in patients with 1st/2nd relapse, harboring PV in BRCA1 RING domain compared to those with PV in the DNA binding domain (DBD) and BRCT domains (12.4 vs. 23.0 months, p = 0.046). No differences in PFS and OS were observed between patients with germline versus somatic BRCA1/2 PV (PFS:14.9 vs.19.3, p = 0.316, OS: not reached vs. 25.8 months; p = 0.224). However, there were significant differences in the reasons for OMT discontinuation between patients with germline and somatic BRCA1/2 PV, primarily due to adverse side effects., Conclusions: In summary, the type and location of BRCA1 and BRCA2 PV provide additional insight into the expected survival outcomes of olaparib MT in PSROC patients., Trial Registration Number: ISRCTN42408038, Name of registry: ISRCTN registry, Date of registration: 24/11/2015., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: We conducted a multi-institutional observational study to investigate whether maintenance hormone therapy following primary treatment of low-grade advanced-stage ovarian cancer (LGSOC) is associated with an overall survival advantage., Methods: We included patients with histologically confirmed stage III or IV LGSOC diagnosed between Jan 1, 2004, and Dec 31, 2019, treated in Commission on Cancer-accredited cancer programs in the US. Patients who received hormone therapy within six months of diagnosis were matched to controls who did not initiate hormone therapy during this timeframe by risk-set propensity score matching. The primary outcome was the risk of death from any cause within five years of initiation of HT or observation., Results: There were 296 patients who initiated maintenance hormone therapy within six months of diagnosis and 2805 potential controls. Patients who received hormone therapy were more often treated in academic medical centers (55% vs. 44%), diagnosed later in the study period (62% vs. 23% diagnosed in 2018-2019), and frequently received no chemotherapy during initial treatment (45% vs. 17%). After risk set propensity score matching, we identified 225 patients treated with HT and 225 untreated controls who were otherwise similar with respect to measured covariates. In the matched cohort, hormone therapy was associated with a reduction in the risk of death (hazard ratio 0.60; 95% CI 0.38-0.94), corresponding to a 60-month survival of 75% compared with 65%., Conclusions: Following primary management of LGSOC, maintenance hormone therapy was associated with improved overall survival compared with observation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Patterns of disease recurrence on poly(ADP-ribose) polymerase inhibitor maintenance therapy are unclear and may affect subsequent treatment. This ad hoc subgroup analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 study evaluated patterns of initial recurrence in patients with advanced ovarian cancer (AOC)., Methods: PRIMA included participants at high risk for disease progression. This ad hoc analysis only evaluated participants randomized to niraparib maintenance without evidence of disease at baseline. The number and site(s) of initial recurrent lesions at investigator-assessed progressive disease (PD) were evaluated., Results: Of the 314 niraparib-treated patients analyzed, 190 developed ≥1 new lesion (median number of new lesions, 1.0; interquartile range, 1-2). In total, 93.2% (177/190) of patients developed 1-3 lesions at first disease progression. The most common sites of recurrence were the peritoneum (30.0% [57/190]), lymph nodes (26.3% [50/190]), and liver (20.5% [39/190]). Similar results were observed when patients with PD were stratified by biomarker status, disease stage at diagnosis, and type of debulking surgery. Patients with homologous recombination-proficient tumors, stage III disease, or a history of primary debulking developed a median of 2.0 new lesions at first progression; patients with homologous recombination-deficient tumors, stage IV disease, or a history of interval debulking developed a median of 1.0 new lesion., Conclusions: Many patients with AOC without lesions at first-line maintenance treatment initiation develop oligometastatic disease at first recurrence. Prospective evaluation is required to determine whether these patients have improved outcomes when local therapies are combined with continuous, systemic, targeted maintenance therapy., Competing Interests: Declaration of competing interest Mitchell R. Kamrava reports receiving book royalties from Springer, serving on data safety and monitoring boards for Alessa and GT Medical Technologies, and receiving consulting fees from Theragenics and Pfizer. Antonio Gonzalez-Martin reports support from GSK; grants from Roche and TESARO; consulting fees from Alkermes, AstraZeneca, Genmab, ImmunoGen, Novartis, Pfizer/Merck, Roche, Sutro, Amgen, Clovis Oncology, GSK, Merck Sharp & Dohme, Oncoinvent, PharmaMar and Sotio; payment or honoraria from AstraZeneca, PharmaMar, Roche and GSK; and travel support from AstraZeneca, Roche, Pharmamar and GSK. Bhavana Pothuri reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Duality Bio, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Seagen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, and VBL Therapeutics; consulting fees from AstraZeneca, BioNtech, Clovis Oncology, Eisai, GOG Foundation, Lily, Merck, Mersana, Seagen, Sutro Biopharma, Tesaro/GSK, Onconova, and Toray; and travel support from GSK and BioNtech. Ignace Vergote reports consulting fees from Agenus, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, GSK, Immunogen, Karyopharm, Mersana, MSD, Molecular Partners, Novocure, Novartis, Oncoinvent, Regeneron, Seagen, Verastem Oncology, Zai Lab, and Zentalis. Whitney Graybill reports institutional research support from NIH/NCI Cancer Center Support Grant (P30 CA008748) and support grants from ArsenalBio, AstraZeneca/Merck, Atara Biotherapeutics/Bayer, Genentech, Genmab, GSK, Gynecologic Oncology Group (GOG) Foundation, Juno Therapeutics, Kite/Gilead, Ludwig Institute for Cancer Research, Lyell Therapeutics, OnCusp Therapeutics, Regeneron, Sellas Life Sciences, Stemcentrx, Syndax, TapImmune, and TCR2 Therapeutics; participation on advisory boards for Bayer, Carina Biotech, Immunogen, Miltenyi, Loxo, Regeneron, R-Pharm, Seattle Genetics, and Tesaro/GSK; personal fees from GOG Foundation; travel fees from Hitech Health; and service as a noncompensated steering committee member for the DUO-O (olaparib) and PRIMA and Moonstone (niraparib) studies. Colleen McCormick reports participation on advisory boards for GSK, Merck, Immunogen and Clovis. Domenica Lorusso reports medical writing support from Clovis Oncology, GSK, MSD and PharmaMar; institutional funding for work in clinical trials from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, and Seagen; consulting fees from Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, PharmaMar, and Seagen; payment or honoraria from AstraZeneca, Clovis Oncology, GSK, MSD, and PharmaMar; travel for AstraZeneca, Clovis Oncology, GSK, PharmaMar, and Roche; participation on Data Safety Monitoring Boards or advisory boards for AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, Merck Serono, MSD, Oncoinvent, PharmaMar, Seagen, and Sutro; and is a member of the board of directors for GCIG (no compensation). Gilles Freyer reports consulting fees and payment/honoraria from GSK. David M. O'Malley reports grants from Ajinomoto, BMS, Cerulean Pharma, GOG Foundation, INC Research, InVentiv Health Clinical, Iovance Biotherapeutics, Ludwig Cancer Research, New Mexico Cancer Care Alliance, PRA International, Serono, Stemcentrx, Tracon Pharmaceuticals, and Yale University; has been a consultant/advisory board member for AbbVie, Ambry, Amgen, Array Biopharma, Clovis, EMD Serono, Ergomed, Janssen/Johnson & Johnson, Myriad Genetics, Novocure, Regeneron, Tarveda, and VentiRx; was a member of a steering committee for Genentech/Roche and Merck; and received personal fees from Agenus, Eisai, GSK and Immunogen. Whitney York is an employee of GSK. Izabela A. Malinowska is an employee of GSK. Bradley J. Monk reports consulting fees from Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Macrogenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL; and payment or honoraria from AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech and Tesaro/GSK., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of age on the efficacy and safety of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy., Methods: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). Patients in the intent-to-treat population were categorized according to age at baseline (<65 years vs ≥65 years), and progression-free survival (PFS), safety, and health-related quality of life (HRQOL) were evaluated for each age subgroup (clinical cutoff date, May 17, 2019). Safety findings were also evaluated according to a fixed starting dose (FSD) or an individualized starting dose (ISD)., Results: Of 733 randomized patients, 289 (39.4%) were ≥65 years (190 niraparib, 99 placebo) at baseline. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) were similar in patients aged <65 years (13.9 vs 8.2 months; HR, 0.61 [0.47-0.81]) and ≥65 years (13.7 vs 8.1 months; HR, 0.53 [0.39-0.74]). The incidences of any-grade and grade ≥3 treatment-emergent adverse events (TEAEs) were similar across age subgroups; in the niraparib arm, TEAEs leading to dose discontinuation occurred in 7.8% of patients <65 years and 18.4% of patients ≥65 years. ISD use lowered the incidence of grade ≥3 thrombocytopenia events in niraparib-treated patients compared with the FSD (<65 years: 42.8% vs 18.0%; ≥65 years 57.0% vs 26.1%). HRQOL was comparable across age subgroups., Conclusion: Niraparib efficacy, safety, and HRQOL were generally comparable across age subgroups, although patients ≥65 years had a higher rate of discontinuations due to TEAEs. ISD use reduced grade ≥3 thrombocytopenia events regardless of age., Competing Interests: Declaration of competing interest Dr. Valabrega reports consulting fees from GSK; honoraria from AstraZeneca, Eisai, GSK, and MSD; travel support from AstraZeneca and PharmaMar; and participation in advisory boards for AstraZeneca, Eisai, GSK, and MSD. Dr. Pothuri reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, GSK, I-Mab, Immunogen, Incyte, Karyopharm, Merck, Mersana, Onconova, SeaGen, Sutro, and Toray; consulting fees from AstraZeneca, GOG Foundation, GSK, Merck, and Seagen; support for attending meetings from GOG Partners; and advisory board fees from Arquer Diagnostics, Atossa, Deciphera, Eisai, Elevar Therapeutics, GOG Foundation, I-Mab, Immunogen, Lily, Merck, Mersana, Natera, Onconova, Regeneron, Sutro Biopharma, Tesaro/GSK, Toray, and VBL Therapeutics. Dr. Oaknin reports institutional grants from AbbVie Deutschland, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics AB, BMS, Clovis Oncology, Eisai, F. Hoffmann–La Roche, Immunogen, MSD de España SA, Millennium Pharmaceuticals, PharmaMar SA, Regeneron Pharmaceuticals, and Tesaro; consulting fees from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, Exelixis, EMD Serono, F. Hoffmann–La Roche, Genmab, GSK, ImmunoGen, Iteos, MSD de España SA, Mersana Therapeutics, Novocure, OncXerna Therapeutics, PharmaMar, Regeneron, Shattuck Labs, Seagen, and Sutro Biopharma; honoraria from Asociación Colombiada de Ginecológos Oncólogos, AstraZeneca, ESO, GSK, Medscape, NSGO, Peerview, and Peervoice; individual travel support from AstraZeneca, PharmaMar, and Roche; and advisory board participation for Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, Exelixis, EMD Serono, F. Hoffmann–La Roche, Genmab, GSK, ImmunoGen, Iteos, MSD de España SA, Mersana Therapeutics, Novocure, OncXerna Therapeutics, PharmaMar, Regeneron, Seagen, Shattuck Labs, and Sutro Biopharma. Dr. Graybill reports consulting and speaker fees from GSK. Dr. Sánchez reports consulting fees from AstraZeneca, GSK, and MSD; honoraria from AstraZeneca, GSK, and MSD; and travel support from AstraZeneca, GSK, and MSD. Dr. McCormick reports personal fees for advisory boards for Clovis, GSK, ImmunoGen, and Merck. Dr. Baurain reports consulting fees from AstraZeneca, BMS, GSK, Immunocore, Merck, MSD, Novartis, Pfizer, Pierre-Fabre, Regeneron, Sanofi, and Sun Pharma. Dr. Tinker reports honoraria from AstraZeneca, Eisai, GSK, and Merck and travel support from GSK. Dr. Denys reports an institutional research grant from Gilead; consulting fees from Gilead and GSK; honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, GSK, Leo Pharma, MSD, and Roche; travel support from AstraZeneca, Gilead, GSK, MSD, Pfizer, PharmaMar, Roche, and Teva; and participation on advisory boards for AstraZeneca, Eli Lilly, Gilead, GSK, Menarini, MSD, and Pfizer. Dr. O'Cearbhaill reports institutional research support from NIH/NCI Cancer Center Support Grant (P30 CA008748) and support grants from AstraZeneca/Merck, Atara Biotherapeutics/Bayer, Genentech, Genmab, GSK, Gynecologic Oncology Group Foundation, Juno Therapeutics, Kite/Gilead, Ludwig Institute for Cancer Research, Regeneron, Sellas Life Sciences, StemcentRx, Syndax, TapImmune, and TCR2 Therapeutics; participating in advisory boards with Bayer, Carina Biotech, Fresenius Kabi, Immunogen, Regeneron, R-Pharm, Seattle Genetics, and Tesaro/GSK; personal fees from GOG Foundation; travel fees from Hitech Health; and service as a noncompensated steering committee member for the DUO-O (olaparib) and PRIMA and Moonstone (niraparib) studies. Dr. Hietanen reports consulting fees from AstraZeneca, Eisai, GSK, and MSD and honoraria from AstraZeneca and GSK. Dr. Moore reports institutional grants from Angle Plc and Fujirebio Diagnostics and personal fees from Fujirebio Diagnostics. Dr. Knudsen has nothing to disclose. Dr. de La Motte Rouge reports receiving consulting fees from AstraZeneca, Clovis Oncology, Eisai, Gilead, GSK, MSD, Novartis, Pfizer, and Sanofi; receiving honoraria from AstraZeneca, GSK, MSD, NetCancer, and Pfizer; and travel support from Gilead, MSD, and Pfizer. Dr. Heitz reports honoraria from AstraZeneca, GSK, Roche, and Tesaro and consulting fees from AstraZeneca, GSK, Roche, and Tesaro. Dr. Levy has nothing to disclose. Dr. Monk reports consulting fees from Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, MacroGenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL and speakers' bureau honoraria from AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, and Tesaro/GSK. Dr. González-Martín reports for different educational or advisory-related activities from Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, Hedera Dx, Immunogen, Illumina, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Roche, Seagen, Sotio, Sutro, Takeda, and Tubulis. Ms. York is a current employee of GSK. Dr. Gupta is a former employee of GSK and Mersana Therapeutics and is currently an employee of Cullinan Oncology., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine patient barriers and facilitators to PARP inhibitor (PARP-I) maintenance therapy in ovarian cancer. PARP-I improves survival in ovarian cancer, but these multi-year therapies cost around $100,000 annually and are under-prescribed., Methods: We recruited patients with ovarian cancer treated with PARP-I maintenance therapy at an academic health system for a semi-structured interview. Patient demographics, including genetics and PARP-I cost, were self-reported. We assessed patient experiences with barriers and facilitators of PARP-I usage. Two team members used a thematic approach to analyze and identify key themes., Results: In May 2022, we interviewed 10 patients (mean age = 65 years; 80% White; 60% with a germline genetic mutation). Patients paid on average $227.50 monthly for PARP-I, straining resources for some participants. While sampled patients were insured, all patients identified having no or inadequate insurance as a major barrier to PARP-I. At the same time, all participants prioritized clinical effectiveness over costs of care. Patients identified PARP-I delivery from specialty pharmacies, separate and different from other medications, as a potential barrier, but each had been able to navigate delivery. Patients expressed significant initial side effects of PARP-I as a potential barrier yet reported clinician communication and prompt dose reduction as facilitating continuation., Conclusions: Patients identified cost, restrictive pharmacy benefits, and initial side effects as barriers to PARP-I usage. Having insurance and a supportive care team were identified as facilitators. Enhancing communication about PARP-I cost and side effects could improve patient experience and receipt of evidence-based maintenance therapy in ovarian cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Smith and Haggerty have received institutional grant funding from GSK unrelated to this work, and Dr. Smith received an honorarium from Total Health Conferences as an invited speaker outside the submitted work. Dr. Rendle reported receiving and grants from Pfizer and AstraZeneca paid to her institution, personal fees from Merck for serving as a scientific consultant, and honoraria and travel paid as invited speaker from MJH Life Sciences outside the submitted work. Dr. Ko received grants from Tesaro, Faeth, and Bristol-Meyers Squibb outside the submitted work. The other authors have no conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To compare oncologic outcomes of secondary cytoreductive surgery (SCS) before and after FDA approval of Poly(ADP-ribose) polymerase inhibitor (PARPi) and bevacizumab maintenance therapies for platinum-sensitive recurrent ovarian cancer (PS-ROC)., Methods: Patients who underwent SCS for first recurrence of PS-ROC from 1/1/2013-1/1/2020 were identified. Exclusion criteria included prior chemotherapy for recurrence, bowel obstruction procedures, and palliative surgery. Data were dichotomized pre/post 1/2017, relative to FDA approval of PARPi and bevacizumab maintenance for ROC. Second progression-free survival (PFS2), the primary endpoint, was estimated using Kaplan-Meier method., Results: Overall, 245 patients underwent SCS-131 (53%) pre- and 114 (47%) post-approval. Most patients had high-grade serous tumors (83% and 90%, respectively; p = 0.13). Deleterious BRCA1/2 alterations were identified in 27% (32/120) and 28% (32/113) of tested patients, respectively (p = 0.88). Disease-free intervals pre- and post-approval were: 6-12 months, 16% and 18%; 12-30 months, 56% and 59%; and >30 months, 28% and 24%, respectively (p = 0.73). Overall, 85% and 86% of patients, respectively, achieved complete gross resection (CGR; p > 0.99). PARPi maintenance use increased from 3.8% to 27% (p < 0.001) following approval, and bevacizumab from 1.5% to 12% (p < 0.001). Median PFS2 was 19 and 20.1 months, respectively. In the post group, 1-year PFS2 rate was 84.5% (95% CI, 75.7-90.4%) for patients with CGR vs 56.2% (95% CI, 29.5-76.2%) for those with residual disease; 3-year PFS2 rates were 31.3% (95% CI, 21.6-41.4%) and 12.5% (95% CI, 2.1-32.8%), respectively (p = 0.001)., Conclusions: CGR during SCS is associated with improved PFS2 compared to suboptimal resection. Prospective randomized trials are warranted to elucidate the role of SCS as more therapeutics become available., Competing Interests: Declaration of competing interest D.S. Chi reports personal fees from AstraZeneca, UptoDate, Biom'Up, Apyx Medical Group, and Verthemia; he also has stock in Verthemia. R.N. Grisham reports honoraria from GlaxoSmithKline (GSK), AstraZeneca, Natera, Springworks, Corcept, MJH, and PER. R.E. O'Cearbhaill reports research funding paid to the institution from Bayer/Celgene/Juno, Arsenalbio, Tesaro/GSK, Merck, Ludwig Cancer Institute, Abbvie/StemCentrx, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Genentech, Alkermes, Kite Pharma, Acrivon and Gynecologic Oncology Foundation, Lyell Immunopharma. She also reports honoraria for lectures from GSK, Curio/Onclive/PER/MJH/Aptitude Health, SITC, Gynecologic Oncology Canada, and the Society of Gynecologic Oncology. She also reports travel/meeting support from Hitech Health, Gathering Around Cancer, Ireland, and the GOG Foundation. She also reports unpaid Steering Committee participation for AstraZeneca, GSK, and Acrivon, as well as unpaid advisory roles for Carina Biotech and Link Therapeutics. She has served on the Advisory Boards of SeaGen, Tesaro/GSK, Regeneron, Immunogenicity, R-Pharm, Fresenius Kabi, Miltenyi, 2seventybio, and Bayer., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy., Methods: Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed., Results: Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified., Conclusion: In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: PARP (poly adenosine diphosphate [ADP]-ribose polymerase) inhibitors are approved as maintenance therapy in platinum sensitive ovarian cancer (OC), in first line and in the recurrent setting, regardless of BRCA mutational status. Real-world data after the introduction of these agents are needed to evaluate whether the benefit observed in phase III randomized clinical trials can be translated into clinical practice. The aim of our study was to provide real-life data on efficacy and safety of niraparib administered as maintenance in platinum sensitive relapsed OC patients (PSROC)., Methods: This retrospective/prospective observational study included relapsed OC patients that received niraparib as maintenance, at the time of platinum sensitive recurrence within the Italian expanded-access program. Clinical data at the time of diagnosis and at the time of recurrence were collected and analyzed. Median progression free survival (PFS) and overall survival (OS) were calculated as the time from start of niraparib treatment to subsequent radiologically confirmed relapse and death or last contact, respectively., Results: Among 304 eligible patients, 260 (85%) had BRCA wild-type tumor and 36. (11.9%) were BRCA mutated. Median PFS was 9.1 months (95% CI: 6.9-11.2) and 10.3 months (95% CI: 7.0-13.5) in the BRCAwt and BRCAmut cohorts, respectively. Furthermore, median OS was 41.7 months (95% CI: 31.6-41.9) and 34.6 months (95% CI: N.E.) in the BRCAwt and BRCAmut cohorts, respectively., Conclusion: Data from this large real-life dataset suggested that maintenance with niraparib in the real-life setting of platinum sensitive OC recurrence is effective and well tolerated., Competing Interests: Declaration of competing interest Marilena Di Napoli reports honoraria from GSK, BSM, MSD; Antonella Savarese reports honoraria from Tesarobio/GSK, AstraZeneca and MSD; Carmine De Angelis reports advisory role from Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Daicii-Sankyo, Gilead and GSK, an speaker honoraria from Roche, Lilly, Novartis, Pfizer, Seagen, GSK, Gilead, and Daichii-Sanchio, and travel grant from Gilead and research support (to the Institutional) from Novartis, Gilead, and Daiichi-Sankyo outside the submitted work; Sandro Pignata reports honoraria from AstraZeneca, MSD, Roche, GSK, Pharmamar and research funding from Roche, MSD, Pfizer, GSK, Astrazeneca; Giovanni Scambia reports consultancy for AstraZeneca, MSD, Covidien AG, a Medtronic company speaker bureau honorarium from Olympus Europa SE & CO. KG, Baxter Healthcare SA, Intuitive Surgical Inc., GlaxoSmithKline S.p.A; Domenica Lorusso reports honoraria from AstraZeneca, Clovis, Genmab, Immunogen, Merck, Roche, Tesaro/GSK, PharmaMar, Consultancy or Advisory Role from AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Amgen, Seagen, PharmaMar, AstraZeneca, Merck Serono, Seagen, Genmab, Oncoinvest, Corcept, Sutro, Speakers' Bureau from AstraZeneca, Clovis Oncology, GSK, MSD, PharmaMar, Research Funding from Clovis (Inst), Merck (Inst), PharmaMar (Inst), Tesaro/GSK (Inst), expert Testimony from Clovis and travel, accommodations, expenses from AstraZeneca, Clovis, PharmaMar, Roche, Tesaro., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy., Methods: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death. HRQoL was assessed as a prespecified secondary end point using patient-reported responses to the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), and EQ-5D-5L questionnaires. Assessments were collected at baseline and every 8 weeks (±7 days) for 56 weeks, beginning on cycle 1/day 1, then every 12 weeks (±7 days) thereafter while the patient received study treatment., Results: Among trial participants (niraparib, n = 487; placebo, n = 246), PRO adherence exceeded 80% for all instruments across all cycles. Patients reported no decline over time in HRQoL measured via EORTC QLQ-C30 Global Health Status/QoL and FOSI overall scores. Scores for abdominal/gastrointestinal symptoms (EORTC QLQ-OV28) and nausea and vomiting, appetite loss, and constipation (EORTC QLQ-C30) were higher (worse symptoms) in niraparib-treated patients than placebo-treated patients; except for constipation, these differences resolved over time. Patients did not self-report any worsening from baseline of fatigue, headache, insomnia, or abdominal pain on questionnaires., Conclusions: Despite some early, largely transient increases in gastrointestinal symptoms, patients with OC treated with niraparib first-line maintenance therapy reported no worsening in overall HRQoL., Competing Interests: Declaration of competing interest Dr. Pothuri reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, GSK, I-Mab, Immunogen, Incyte, Karyopharm, Merck, Mersana, Onconova, Seagen, Sutro Biopharma, and Toray; consulting fees from AstraZeneca, GSK, GOG Foundation, Merck, and Seagen; support for attending meetings from GOG Partners; advisory board fees from Arquer Diagnostics, Atossa, Clovis Oncology, Deciphera, Eisai, Elevar Therapeutics, GOG Foundation, I-Mab, Immunogen, Lily, Merck, Mersana, Natera, Onconova, Regeneron, Sutro Biopharma, Tesaro/GSK, Toray, and VBL Therapeutic. Dr. Han has nothing to disclose. Dr. Chase reports consultant fees from AstraZeneca and GSK, and honoraria from AstraZeneca, GSK, Immunogen, and Seagen/Genmab. Dr. Heitz reports honoraria from AstraZeneca, GSK, Roche, and Tesaro; consulting fees from AstraZeneca, GSK, Roche, and Tesaro. Dr. Burger reports receiving travel support from Genentech and Mersana Therapeutics, stock from Genentech and Mersana Therapeutics, and is an employee of Genentech and Mersana Therapeutics. Dr. Gaba reports consulting fees, advisory board, and honoraria fees from AstraZeneca, Clovis Oncology, GSK, MSD, and PharmaMar, and support for attending meetings from AstraZeneca, Clovis Oncology, GSK, and MSD. Dr. Van Le has nothing to disclose. Dr. Guerra reports AstraZeneca, Clovis Oncology, GSK, Merck, Pharmamar, Roche, and Tesaro; honoraria from AstraZeneca, Clovis Oncology, GSK/Tesaro, and Merck; payment for expert testimony from AstraZeneca, Clovis Oncology, GSK, Merck, Tesaro; travel support from GSK, Roche, and Tesaro; advisory board participation for AstraZeneca, GSK, Merck, and Tesaro. Dr. Bender reports institutional grants from AbbVie, AstraZeneca, Clovis Oncology Inc., Genentech, MSD, and Tesaro. Dr. Korach serves in a leadership role for ISGO. Dr. Cloven reports advisory board fees from Aadii, GSK, Kartos 2022, Novita Pharmaceuticals 2023, Tarveda Therapeutics, Toray, Umoja 2022, and Zentalis. Dr. Churruca reports payment for expert testimony from PharmaMar and support for attending meetings from GSK, and MSD. Dr. Follana reports payment for expert testimony from AstraZeneca, Clovis, Daiichi, GSK, and Novartis; and support for attending meetings from AstraZeneca, Daiichi, GSK, and Novartis. Dr. DiSilvestro reports consulting fees from AstraZeneca, GSK, and Immunogen; travel support from AstraZeneca; and leadership roles in the GOG Foundation Board of Directors and NRG Oncology Board of Directors. Dr. Baurain reports consulting fees from AstraZeneca, Bristol-Myers Squibb, GSK, Immunocore, Merck, MSD, Novartis, Pfizer, Pierre-Fabre, Regeneron, Sanofi, and Sun Pharma. Dr. Jardon has nothing to disclose (deceased). Dr. Pisano has nothing to disclose. Dr. Peen has nothing to disclose. Dr. Mäenpää reports honoraria from AstraZeneca, Eisai, and GSK. Dr. Gupta was an employee of GSK at the time the analysis was conducted; currently an employee of Mersana Therapeutics. Dr. Bacqué was an employee of GSK at the time the analysis was conducted; currently an employee of Repare Therapeutics. Dr. Li was an employee of GSK at the time the analysis was conducted and reports GSK stock ownership; currently an employee of Adagio Therapeutics. Ms. Compton is a former employee of GSK and currently receiving consulting fees from GSK. Dr. Antonova is a former employee of GSK. Dr. Monk reports consulting fees from Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, MacroGenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL; and speakers' bureau honoraria from AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, and Tesaro/GSK. Dr. González-Martín reports manuscript funding from GSK; research/grant funding from Roche and Tesaro/GSK; advisory/consulting fees from Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, HederaDx, ImmunoGen, Illunina, MacroGenics, Mersana, MSD, Novartis, Novocure, Oncoinvent, Pfizer/Merck, PharmaMar, Roche, Seagen, Sotio, Sutro, Takeda, and Tubuli; speaker bureau fees from AstraZeneca, Clovis Oncology, GSK, PharmaMar, and Roche; and support for attending meetings from AstraZeneca, GSK, PharmaMar, and Roche., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Inhibitors of poly(ADP-ribose) polymerase (PARP) and angiogenesis have demonstrated single-agent activity in women with advanced ovarian cancer. Recent studies have aimed to establish whether combination therapy can augment the response seen with PARP inhibitors or antiangiogenic agents alone. This review provides an overview of PARP inhibitors and antiangiogenics as monotherapy in women with advanced ovarian cancer, explores potential mechanisms of action of PARP inhibitor and antiangiogenic combination treatments, reviews efficacy and safety data from trials evaluating this combination, and outlines ongoing and future trials evaluating this combination, discussing these in the context of the current and future treatment landscape for women with advanced ovarian cancer. Sentinel studies evaluating PARP inhibitor (n = 8), antiangiogenic (n = 4), and combination (n = 7) therapy were identified in women with newly diagnosed (n = 7) and recurrent (n = 12) ovarian cancer. PARP inhibitors included olaparib (n = 9), niraparib (n = 4), rucaparib (n = 1), and veliparib (n = 1). Antiangiogenic agents included bevacizumab (n = 7) and cediranib (n = 4). PARP inhibitors combined with antiangiogenics demonstrated efficacy based on objective response rates and progression-free survival (PFS) in the relapsed disease setting. Maintenance therapy with the PARP inhibitor, olaparib, plus antiangiogenic therapy offered a significant PFS benefit versus the antiangiogenic alone in women with newly diagnosed advanced ovarian cancer who tested positive for homologous recombination deficiency. Combination therapy was tolerated, with no new safety signals reported compared with monotherapy trials. PARP inhibitors and antiangiogenics have changed the landscape of ovarian cancer treatment. The PARP inhibitor plus antiangiogenic combination is a novel treatment option that appears promising in the first-line advanced and recurrent ovarian cancer settings, although the role of this combination in recurrent disease requires further elucidation. Defining which patients are candidates for monotherapy or combination therapy is critical, taking into consideration safety profiles of therapies alone or in combination, and how these treatments should be sequenced in clinical practice., Competing Interests: Declaration of Competing Interest AAS: reports institutional support for clinical research from AbbVie and National Cancer Trial Network; institutional support for clinical research and personal fees from Advisory Boards from AstraZeneca, Clovis Oncology, Roche/Genentech and GSK/Tesaro; and personal fees for an Advisory Board from Myriad Genetics relevant to the content in this manuscript. She has received institutional support from Amgen, Astellas Pharma Inc., Astex Pharmaceuticals Inc., Boehringer Ingelheim, Bristol-Myers Squibb Co., Eisai, Endocyte, Exelixis, Immutep Ltd., Incyte, Merck, PharmaMar, Seattle Genetics, Inc. and VBL Therapeutics; personal fees for Advisory Boards from Aravive, Cordgenics, Eisai, Janssen/Johnson & Johnson, Merck, Mersana and Oncoquest; and participated in Steering Committees (noncompensated) for Roche/Genentech and VBL Therapeutics outside the submitted work. DMOM: reports personal fees and institutional support for clinical research from AstraZeneca, Clovis, Tesaro, Immunogen, Janssen/Johnson & Johnson, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOG Foundation, Eisai, Agenus, GSK and Merck; personal fees from Ambry, Myriad Genetics, and Tarveda; institutional support for clinical research from VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc., CERULEAN PHARMA, Bristol-Myers Squibb Co., Serono Inc., TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc., inVentiv Health Clinical, Iovance Biotherapeutics, Inc. and PRA Intl. AKS: has consulted for Merck and Kiyatec, is a shareholder in BioPath, and has received research support from M-Trap. SNW: reports personal fees for consulting from Agenus, AstraZeneca, Circulogene, Clovis Oncology, Merck, Novartis, Pfizer, Roche/Genentech, GSK/Tesaro, Eisai and Zentalis; and research funding to her institution from ArQule, AstraZeneca, Bayer, Bio-Path, Clovis Oncology, Cotinga Pharmaceuticals, Novartis, Roche/Genentech and GSK/Tesaro. JFL: reports advisory board participation for AstraZeneca, Clovis, Genentech, Merck, Regeneron and Tesaro/GSK; consulting for Genentech; and funding to her institution for study conduct as Principal Investigator on trials from 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, CytomX Therapeutics, Genentech, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro and Vigeo Therapeutics., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors report the following conflicts of interest. The remaining authors report no conflicts of interest. Thomas J. Herzog: Honoraria/Reimbursement and Scientific advisory board AstraZeneca, Caris, Clovis, Genentech, GSK, Johnson and Johnson, Merck. Robert L. Coleman: Consulting, Grant, Honoraria/Reimbursement: Abbvie, Aravive, AstraZeneca, Clovis, Eisai, Genmab, GSK / Tesaro, Janssen, Merck, Oncomed, Mateon, Novocure, OncoQuest, Oncosec, Roche / Genentech, V-Foundation. Bradley J. Monk: Consulting and Honoraria/Reimbursement or Speakers' Bureau(s): Abbvie, Advaxis, Agenus, Amgen, Aravive, AstraZeneca, Asymmetric, Therapeutics, Boston Biomedical, ChemoCare, ChemoID, Circulogene, Clovis, Conjupro, Eisai, Geistlich, Genmab/Seattle Genetics: GOG Foundation, ImmunoGen, Immunomedics, Incyte, Janssen/Johnson&Johnson, Laekna Health Care, Mateon (formally Oxigene), Merck, Mersana, Myriad, Nucana, Oncomed, Oncoquest, Oncosec, Perthera, Pfizer, Precision Oncology, Puma, Regeneron, Roche/Genentech, Samumed, Takeda, TESARO/GSK, VBL, Vigeo. John K. Chan: Consulting and Honoraria/Reimbursement or Speakers' Bureau(s): Acerta, Aravive, AstraZeneca, Biodesix, Clovis, Eisai, Janssen / J and J, Oxigene / Mateon, Roche / Genentech, Glaxosmithkline / Tesaro.

Objectives: Clinical trials evaluating universal PARP inhibitor (PARPi) frontline maintenance therapy for advanced stage ovarian cancer have reported progression-free survival (PFS) benefit. It is unclear whether PARPi maintenance therapy will universally enhance value (clinical benefits relative to cost of delivery). We compared a "PARPi-for-all" to a biomarker-directed frontline maintenance therapy approach as a value-based care strategy., Methods: The cost of two frontline PARPi maintenance strategies, PARPi-for-all and biomarker-directed maintenance, was compared using modified Markov decision models simulating the study designs of the PRIMA, VELIA, and, PAOLA-1 trials. Outcomes of interest included overall costs and incremental cost-effectiveness ratios (ICERs) reported in US dollars per quality adjusted progression-free life-year (QA-PFY) gained., Results: PARPi-for-all was more costly and provided greater PFS benefit than a biomarker-directed strategy for each trial. The mean cost per patient for the PARPi-for-all strategy was $166,269, $286,715, and $366,506 for the PRIMA, VELIA, and PAOLA-1 models, respectively. For the biomarker-directed strategy, the mean cost per patient was $98,188, $167,334, and $260,671 for the PRIMA, VELIA, and PAOLA-1 models. ICERs of PARPi-for-all compared to biomarker-directed maintenance were: $593,250/QA-PFY (PRIMA), $1,512,495/QA-PFY (VELIA), and $3,347,915/QA-PFY (PAOLA-1). At current drug pricing, there is no PFS improvement in a biomarker negative cohort that would make PARPi-for-all cost-effective compared to biomarker-directed maintenance., Conclusions: This study highlights the high costs of universal PARPi maintenance treatment, compared with a biomarker-directed PARPi strategy. Maintenance therapy in the front-line setting should be reserved for those with germline or somatic HRD mutations until the cost of therapy is significantly reduced., Competing Interests: Declaration of Competing Interest Dr. Secord reports grants from AbbVie, grants from Amgen, grants from Astellas Pharma Inc., grants from Astex Pharma Inc., grants and personal fees from Aztra Zeneca, grants from Boehringer Ingelheim, grants from Bristol Myers Squibb, grants and personal fees from Clovis, grants and personal fees from Eisai, grants from Endocyte, grants from Exelixis, grants from Immutep, grants from Incyte, grants and personal fees from Merck, grants from PharmaMar, grants and personal fees from Roche/Genetech, grants from Seattle Genetics, grants and personal fees from Tesaro/GSK, grants from VBL therapeutics, grants from National Cancer Trial Network, personal fees from Aravive, personal fees from Cordgenics, personal fees from Johnson & Johnson, personal fees from Mersana, personal fees from Myriad, personal fees from Oncoquest. Dr. Myers reports personal fees from Merck, Inc., personal fees from AbbVie, Inc., personal fees from Bayer, Inc. Dr. Havrilesky reports grants from Astra Zeneca, grants from Tesaro. Dr. Moss receives funding from the NIH (K12HD043446). The remainder of the authors have nothing to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in heavily pretreated patients and as maintenance treatment in patients with newly-diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy. We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial., Methods: This multicenter, double-blind, randomized, controlled phase III trial evaluated the efficacy and safety of niraparib for the treatment of recurrent ovarian cancer. Patients were randomly assigned 2:1 to receive either once-daily niraparib 300 mg or placebo. Two independent cohorts were enrolled based on germline BRCA mutation status. The primary endpoint was progression-free survival, reported previously. Long-term safety data were from the most recent data cutoff (September 2017)., Results: Overall, 367 patients received niraparib 300 mg once daily. Dose reductions due to TEAEs were highest in month 1 (34%) and declined every month thereafter. Incidence of any-grade and grade ≥ 3 hematologic and symptomatic TEAEs was also highest in month 1 and subsequently declined. Incidence of grade ≥ 3 thrombocytopenia decreased from 28% (month 1) to 9% and 5% (months 2 and 3, respectively), with protocol-directed dose interruptions and/or reductions. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) were reported in 2 and 6 niraparib-treated patients, respectively, and in 1 placebo patient each. Treatment discontinuations due to TEAEs were <5% in each month and time interval measured., Conclusion: These data demonstrate the importance of appropriate dose reduction according to toxicity criteria and support the safe long-term use of niraparib for maintenance treatment in patients with recurrent ovarian cancer., Trial Registration: ClinicalTrials.gov identifier: NCT01847274., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

PARP inhibitors (PARPi) have shown have activity in the treatment of ovarian cancer. Previous studies documented activity in patients with germline (gBRCA) and tumor (tBRCA) BRCA mutations (BRCAm) for treatment in lieu of chemotherapy as well as in recurrent ovarian cancer as maintenance therapy. The recent data from four randomized phase 3 trials have established an important role for frontline PARPi maintenance therapy in ovarian cancer. While SOLO-1 only included BRCAm patients, PRIMA, VELIA, and PAOLA-1 enrolled broader patient populations. The magnitude of benefit of PARPi in these studies was consistently greatest in the BRCAm patients (germline or tumor). PARPi treatment also improved PFS in the HRD cohort but to a lesser degree than in patients with BRCAm. In secondary analyses, the overall impact of PARPi treatment in HR proficient patients, which comprise about 50% of ovarian cancers, was more limited than in the other subgroups. Data for overall survival, also a secondary endpoint, is currently immature for these four trials. Fatigue, hematologic, and GI toxicities are the most commonly noted adverse events with PARPi therapy. The recent FDA approvals of PARPi in the maintenance setting will enable clinicians to incorporate these into frontline armamentarium of ovarian cancer treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to investigate the correlation between BRCA mutational status and response to bevacizumab in a large advanced ovarian cancer (AOC) series., Methods: This is a multicenter, retrospective case-control study including upfront AOC treated between January 2015 and June 2019. The main inclusion criteria were: having received three weekly carboplatin-paclitaxel as first-line treatment, with or without Bevacizumab maintenance, knowledge of the BRCA mutational status., Results: Overall, 441 patients were included; 183 (41.5%) patients received bevacizumab (Cases), and 258 (58.5%) did not receive it (Controls). The BRCA mutated patients (BRCAmut) were 58 (39%) in the Cases group and 90 (34.9%) in the Controls group (p = .77). Patients who received bevacizumab had a significant 4-months increase in median progression free survival (mPFS: 21 vs. 17 months, p = .033). Concerning BRCAmut patients, no differences were shown between those who received bevacizumab or not in terms of mPFS (24 vs. 22 months, p = .3). Conversely, in BRCA wild-type (BRCAwt) population bevacizumab administration significantly prolonged mPFS (20 vs 15 months, p = .019). At multivariate analysis, independent factors of prolonged PFS were BRCA status (OR = 0.60), having received PDS (OR = 0.69), and complete cytoreduction (OR = 0.50), but not the bevacizumab administration (OR = 0.83, p = .22)., Conclusions: No evidence of oncological benefit in terms of PFS and OS related to bevacizumab maintenance therapy was found in BRCAmut patients. Differently, BRCAwt patients seem to benefit from antiangiogenic treatment in terms of mPFS., Competing Interests: Declaration of Competing Interest CC, EG, GB, LV, VC, AD, AF have nothing to disclose. DL reports grants and personal fees from ROCHE, grants and personal fees from TESARO, grants and personal fees from CLOVIS, grants and personal fees from MERCK, grants and personal fees from PHARMAMAR, personal fees from IMMUNOGEN, personal fees from GENMAB, personal fees from AMGEN, personal fees from ASTRA ZENECA, outside the submitted work. CM reports grants and personal fees from CLOVIS, grants and personal fees from GSK, personal fees from ROCHE, grants and personal fees from ARQUER DIAGNOSTCS, personal fees from PHARMAMAR, outside the submitted work. GF reports grants and personal fees from CLOVIS, grants and personal fees from TESARO, personal fees from PHARMAMAR, outside the submitted work. FR reports other from ROCHE, personal fees from TESARO/GSK, outside the submitted work. GS reports personal fees from ROCHE, personal fees from Clovis Oncology, personal fees from Astra Zeneca, personal fees from PharmaMar, personal fees from Tesaro, outside the submitted work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In the phase 3 trial ARIEL3, maintenance treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib provided clinical benefit versus placebo for patients with recurrent, platinum-sensitive ovarian cancer. Here, we evaluate the impact of age on the clinical utility of rucaparib in ARIEL3., Methods: Patients with platinum-sensitive, recurrent ovarian carcinoma with ≥2 prior platinum-based chemotherapies who responded to their last platinum-based therapy were enrolled in ARIEL3 and randomized 2:1 to rucaparib 600 mg twice daily or placebo. Exploratory, post hoc analyses of progression-free survival (PFS), patient-centered outcomes (quality-adjusted PFS [QA-PFS] and quality-adjusted time without symptoms or toxicity [Q-TWiST]), and safety were conducted in three age subgroups (<65 years, 65-74 years, and ≥75 years)., Results: Investigator-assessed PFS was significantly longer with rucaparib than placebo in patients aged <65 years (rucaparib n = 237 vs placebo n = 117; median, 11.1 vs 5.4 months; hazard ratio [HR]: 0.33 [95% confidence interval (95% CI) 0.25-0.43]; P < 0.0001) and 65-74 years (n = 113 vs n = 64; median, 8.3 vs 5.3 months; HR 0.43 [95% CI 0.29-0.63]; P < 0.0001) and numerically longer in patients aged ≥75 years (n = 25 vs n = 8; median, 9.2 vs 5.5 months; HR 0.47 [95% CI 0.16-1.35]; P = 0.1593). QA-PFS and Q-TWiST were significantly longer with rucaparib than placebo across all age subgroups. Safety of rucaparib was generally similar across the age subgroups., Conclusions: Efficacy, patient-centered outcomes, and safety of rucaparib were similar between age subgroups, indicating that all eligible women with recurrent ovarian cancer should be offered this therapeutic option, irrespective of age. https://clinicaltrials.gov/ct2/show/NCT01968213., Competing Interests: Declaration of competing interest Nicoletta Colombo: Served in a consulting or advisory role for Clovis Oncology, AstraZeneca, BIOCAD, Pfizer, PharmaMar, Roche, and Tesaro. Amit M. Oza: Served on advisory boards for Clovis Oncology, Amgen, AstraZeneca, GlaxoSmithKline, and Immunovaccine. Domenica Lorusso: Served in a consulting or advisory role for Clovis Oncology, AstraZeneca, ImmunoGen, Merck, PharmaMar, Roche, Takeda, and Tesaro and received support for travel or accommodation from PharmaMar and Roche. Carol Aghajanian: Served on a steering committee for Clovis Oncology, AbbVie, Genentech, and Mateon Therapeutics; served on advisory boards for Clovis Oncology, Cerulean Pharma, Eisai/Merck, ImmunoGen, and Tesaro; received research grants from Clovis Oncology, AbbVie, AstraZeneca, and Genentech; and received honoraria from Clovis Oncology, Cerulean Pharma, Eisai/Merck, ImmunoGen, Mateon Therapeutics, and Tesaro. Ana Oaknin: Served on advisory boards for Clovis Oncology, AstraZeneca, ImmunoGen, Genmab/Seattle Genetics, PharmaMar, Roche, and Tesaro; received support for travel or accommodation from Clovis Oncology, AstraZeneca, PharmaMar, and Roche; and received research grants from Clovis Oncology, AbbVie Deutschland, Ability Pharmaceuticals, Advaxis, Aeterna Zentaris, Amgen SA, Aprea Therapeutics AB, Bristol-Myers Squibb, Eisai, F. Hoffmann-La Roche, ImmunoGen, Merck Sharp & Dohme de España SA, Millennium Pharmaceuticals, PharmaMar, Regeneron Pharmaceuticals, and Tesaro. Andrew Dean: Served in a consulting or advisory role for Precision Oncology Australia, Shire Pharmaceuticals, and Specialised Therapeutics Australia. Johanne I. Weberpals: Received research support from AbbVie and AstraZeneca and served on advisory boards for AstraZeneca. Andrew R. Clamp: Served on advisory boards for AstraZeneca; received research funding from Clovis Oncology and AstraZeneca; and received support for travel and accommodation for congress attendance from Clovis Oncology, AstraZeneca, and Roche. Giovanni Scambia: Served in a consulting or advisory role for Clovis Oncology, AstraZeneca, PharmaMar, Roche, and Tesaro. Alexandra Leary: Served on advisory boards for Clovis Oncology, AstraZeneca, BIOCAD, GamaMabs, Genmab/Seattle Genetics, Merck Sharp & Dohme, Pfizer, PharmaMar, and Tesaro; received support for travel and accommodation from Clovis Oncology, AstraZeneca, Roche, and Tesaro; and reports institutional research grant support from Clovis Oncology, AstraZeneca, GamaMabs, Inivata, Merck Sharp & Dohme, Merus, Sanofi, and Tesaro. Robert W. Holloway: Served on speakers bureaus for Clovis Oncology, AstraZeneca, and Tesaro. Margarita Amenedo Gancedo: Served on advisory boards for Clovis Oncology and on speakers bureaus for AstraZeneca, PharmaMar, and Roche. Peter C. Fong: Served on advisory boards for Clovis Oncology and AstraZeneca and received honoraria from AstraZeneca. Jeffrey C. Goh: Served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb and Tesaro; served on speakers bureaus for Ipsen and Merck Sharp & Dohme; and received support for travel or accommodation from Astellas, AstraZeneca, and Bristol-Myers Squibb. David M. O'Malley: Served on advisory boards for Clovis Oncology, AbbVie, AstraZeneca, Eisai, Genentech/Roche, Genelux, Iovance Biotherapeutics, Janssen, Novocure, Regeneron, and Tesaro; has served on steering committees for Clovis Oncology, Agenus, Amgen, and Novocure; has served as a consultant for AbbVie, Ambry, AstraZeneca, Genentech/Roche, Gynecologic Oncology Group Foundation, and Tesaro; has given a presentation on ovarian cancer at the National Comprehensive Cancer Network; and his institution has received research support from Clovis Oncology, AbbVie, Agenus, Amgen, Ajinomoto, Array BioPharma, AstraZeneca, Bristol-Myers Squibb, Cerulean Pharma, Eisai, EMD Serono, ERGOMED Clinical Research, Genentech, Gynecologic Oncology Group, INC Research, inVentiv Health Clinical, Iovance Biotherapeutics, Janssen Research and Development, Ludwig Institute for Cancer Research, New Mexico Cancer Care Alliance, Novocure, PRA International, Regeneron Pharmaceuticals, Serono, Stemcentrx, Tesaro, TRACON Pharmaceuticals, VentiRx, and Yale University. Deborah K. Armstrong: Served as a scientific advisor for Morphotek and received research funding from Clovis Oncology, Advaxis, AstraZeneca, Pfizer, Syndax, and Tesaro. Susana Banerjee: Served on advisory boards and received honoraria from Clovis Oncology, AstraZeneca, PharmaMar, Seattle Genetics, and Tesaro; received honoraria from Merck Serono and Roche; and received support for travel or accommodation from NuCana and Tesaro. Jesus García-Donas: Received research funding from AstraZeneca, Pierre Fabre, and Pfizer; received personal fees from Clovis Oncology, Astellas, Pierre Fabre, and Pfizer; and received nonfinancial support from Astellas, Pierre Fabre, and Pfizer. Elizabeth M. Swisher: Has nothing to disclose. Juliette Meunier: Employee of Modus Outcomes, which was contracted by Clovis Oncology to conduct these analyses. Terri Cameron, Lara Maloney, Sandra Goble, and Josh Bedel: Employees of Clovis Oncology and may own stock or have stock options in that company. Jonathan A. Ledermann: Received lecture fees from Clovis Oncology, AstraZeneca, Merck/Merck Sharp & Dohme, Pfizer, and Tesaro; served on advisory boards for Clovis Oncology, Artios Pharma, AstraZeneca, Cristal Therapeutics, Merck/Merck Sharp & Dohme, Pfizer, Regeneron, Roche, Seattle Genetics, and Tesaro; and received research grants from AstraZeneca and Merck/Merck Sharp & Dohme. Robert L. Coleman: Reports grants from Clovis Oncology, AstraZeneca, Gateway Foundation, Janssen, Judy Reis/Albert Pisani, MD, Ovarian Cancer Research Fund, Merck, National Institutes of Health, Roche/Genentech, and V-Foundation; has served as an advisor to Clovis Oncology, Agenus, AstraZeneca, GamaMabs, Genmab, Janssen, OncoQuest, Pfizer (Medivation), Regeneron, Roche/Genentech, and Tesaro; and has an endowment as the Ann Rife Cox Chair in Gynecology., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the cost-effectiveness of olaparib, a PARP inhibitor, as maintenance therapy for platinum-sensitive (PS) recurrent ovarian cancer., Methods: Two separate decision analysis models compared the cost of observation versus olaparib maintenance therapy in patients with PS recurrent ovarian cancer, one for patients with a germline BRCA1/2 mutation and one for patients with wild-type BRCA1/2. Patients received six cycles of paclitaxel and carboplatin. Drug costs were estimated using 2014-2015 wholesale acquisition costs. The cost of olaparib was estimated at $13,440 per month. Rate of germline BRCA1/2 mutation was estimated at 20%. Progression-free survival was determined from published data. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were calculated. A sensitivity analysis estimated the cost at which olaparib would be cost-effective., Results: We estimated that there were 5549 patients diagnosed with PS recurrent ovarian cancer in the United States annually. The cost of observation in 1110 patients with a BRCA1/2 mutation was $5.5 million (M) versus $169.2M for maintenance therapy with olaparib. The ICER for olaparib maintenance therapy in patients with a BRCA mutation was $258,864 per PF-LYS. If the cost of olaparib was decreased to $2500 per month, the ICER was $49,584. For the 4439 patients with wild-type BRCA, the cost of maintenance therapy was $444.2M; the ICER was $600,552 per PF-LYS., Conclusions: For patients with a germline BRCA1/2 mutation, maintenance therapy with olaparib is not cost-effective with an ICER of $258,864 per PF-LYS. To achieve an ICER of less than $50,000, the cost of olaparib should be $2500 or less per month. For wild-type BRCA1/2 patients, maintenance therapy with olaparib is not cost-effective., (Copyright © 2015 Elsevier Inc. All rights reserved.)