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Objective: The CHAR1ZMA study described real-world duration of first-line maintenance niraparib monotherapy among patients with epithelial ovarian cancer., Methods: This retrospective study used a US nationwide, electronic-health-record-derived, de-identified database. Eligible patients were aged ≥18 years with epithelial ovarian cancer who initiated first-line maintenance niraparib monotherapy (January 2017-December 2022 [inclusive]) following first-line platinum-based chemotherapy. Niraparib monotherapy duration was measured as the time to treatment discontinuation, estimated using Kaplan-Meier methodology, overall and stratified by treatment duration (early discontinuers [≤90 days]; non-early discontinuers [>90 days or did not discontinue]). Analyses were repeated in a sub-group of patients with homologous recombination-deficient tumors., Results: Toxicity was the most common reason for niraparib discontinuation among early discontinuers (67.7%) and was less frequent among non-early discontinuers (18.1%). Dose modifications were less frequent among early discontinuers (29.8%) than non-early discontinuers (53.6%). Disease progression was the most common reason for niraparib discontinuation among non-early discontinuers (74.8%) and was less frequent among early discontinuers (30.4%). The observed median treatment duration was 7.2 months (95% CI 6.0 to 8.1) overall (N = 560) and was 4.5 months longer among non-early discontinuers (11.7 months [95% CI 9.8 to 14.7]; n = 399). In the homologous recombination-deficient sub-group (n = 144), the observed median treatment duration was 11.6 months (95% CI 7.8. to 16.1) and was 5.1 months longer among non-early discontinuers (16.7 months [95% CI 12.0 to 22.8]; n = 114)., Conclusion: In this real-world study of patients with epithelial ovarian cancer receiving first-line maintenance niraparib monotherapy, drug toxicity was the most common reason for treatment discontinuation in early discontinuers. Effective and early clinical management of drug toxicity may help mitigate these adverse events, allowing patients to remain on niraparib maintenance treatment longer and experience the potential full therapeutic benefit., Competing Interests: Declaration of Competing Interests FJB has received financial compensation for serving on advisory boards for GSK, AstraZeneca, Clovis Oncology, ImmunoGen, Merck, Eisai, Myriad Genetics, Daiichi Sankyo, BioNTech, and EMD Serono. Her institution has received financial support for her role as a principal investigator for Natera, Merck, Eisai, Clovis Oncology, ImmunoGen, and BeiGene. TACB, JL, JH, JMS, JAH, JP, and AG are employees of and may hold financial equities in GSK. Furthermore, JP owns stock in Boston Scientific and the UnitedHealth Group. RS has received financial compensation for serving on advisory boards for Merck, Seagen, and Mersana Therapeutics; speakers' bureaus for Merck; and writing for UpToDate. She has also served as a principal investigator for Genentech., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To assess real-world progression-free survival (rwPFS) and time to next treatment (rwTTNT) among patients with epithelial ovarian cancer (EOC) who received first-line maintenance (1LM) niraparib monotherapy., Patients & Methods: In this US-nationwide, electronic health record-derived, deidentified database study, eligible patients with EOC initiated 1LM niraparib monotherapy (1 January 2017-1 December 2022) following first-line platinum-based chemotherapy. Median rwPFS and rwTTNT were estimated with Kaplan-Meier methodology overall and in a homologous recombination-deficient (HRd) subgroup (further stratified as BRCA wild-type [ BRCA wt] or BRCA -mutated [ BRCA m])., Results: Observed median rwPFS was 11.4 (95% CI, 10.1-12.7) months overall ( N  = 560), 18.2 (95% CI, 13.9-24.2) months for the HRd subgroup ( n  = 144), and 25.4 (95% CI, 15.9-not reached) and 14.2 (95% CI, 8.6-18.6) months for HRd patients with BRCA m and BRCA wt tumors, respectively. Observed median rwTTNT was 12.4 (95% CI, 11.5-13.8) months overall, 19.6 (95% CI, 14.9-23.9) months for the HRd subgroup, and 24.9 (95% CI, 16.0-not reached) and 15.1 (95% CI, 10.3-19.8) months for HRd patients with BRCA m and BRCA wt tumors, respectively., Conclusions: The real-world observed median rwPFS and rwTTNT were longer for patients with EOC who received 1LM niraparib monotherapy in the HRd subgroup (specifically for the BRCA m subgroup).

Introduction: Niraparib first-line maintenance (1LM) therapy has demonstrated clinical benefit for patients with ovarian cancer (OC) in clinical trial and real-world settings, but data on factors associated with real-world patient outcomes remain limited. This analysis identified patient characteristics associated with time to next treatment (TTNT), a proxy for real-world progression-free survival, in patients with OC treated with 1LM niraparib monotherapy., Methods: This retrospective observational study used a USA nationwide electronic health record-derived deidentified database and included adult patients diagnosed with OC who initiated 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Patients were followed until the earliest occurrence of last clinical activity, death, or end of study period. TTNT was measured from 1LM niraparib initiation to the start of second-line treatment or death. Cox proportional hazards models assessed univariable and multivariable associations between baseline characteristics and TTNT., Results: Of 7872 patients diagnosed with OC, 526 met the eligibility criteria and were included in this analysis. Median (IQR) duration of follow-up was 14.1 (7.4-23.6) months. In univariable analyses, age, BRCA/homologous recombination deficiency (HRD) status, socioeconomic status, stage at initial diagnosis, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT and were introduced into the multivariable model with other clinically relevant variables. In the multivariable analysis, BRCA/HRD status, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT after covariate adjustment. Conversely, age, Eastern Cooperative Oncology Group performance status, disease stage, niraparib starting dose status, and first-line bevacizumab use were not associated with observed TTNT., Conclusion: This real-world, retrospective, observational analysis offers valuable insights on prognostic factors associated with TTNT in patients with OC treated with 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Future studies are needed to examine how additional patient characteristics associated with clinical outcomes may guide treatment decisions and improve outcomes., (© 2024. The Author(s).)

Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) are metabolized either via carboxylesterase (niraparib) or cytochrome P450 (CYP) enzymes (olaparib and rucaparib). Patients with advanced epithelial ovarian cancer (aOC) who receive concomitant medication metabolized by the CYP system may be at risk of drug-drug interactions impacting PARPi efficacy and tolerability. This study investigated CYP inhibitor/inducer treatment patterns in the first-line maintenance (1Lm) setting for patients with aOC. This retrospective cohort study used de-identified databases of US patients with aOC. Eligible patients were aged ≥18 years, diagnosed with aOC between January 2015-March 2021, and received CYP inhibitors/inducers during 1Lm PARPi initiation or the eligibility window (90 days before to 120 days after first-line platinum-based therapy ended [index]). Patients were either prescribed 1Lm PARPi monotherapy (PARPi cohort) or were not prescribed any 1Lm therapy within 120 days post-index (PARPi-eligible cohort). Strong/moderate CYP inhibitors/inducers were defined as area under the plasma concentration-time curve ratio (AUCR) ≥2 or clearance ratio (CL) ≤0.5 (inhibitors), and AUCR ≤0.5 or CL ratio ≥2 (inducers). Of 1411 patients (median age 63), 158 were prescribed PARPis and 1253 were PARPi-eligible. Among the PARPi cohort, 46.2%, 48.7%, and 5.1% were prescribed niraparib, olaparib, and rucaparib, respectively. For patients prescribed olaparib or rucaparib, 42.4% also received strong and/or moderate CYP inhibitors/inducers. This real-world study indicated a considerable proportion of patients received strong and/or moderate CYP inhibitors/inducers and were prescribed PARPis metabolized by the CYP system. Understanding potential impacts of concomitant CYP inhibitors/inducers on PARPi efficacy and safety is warranted., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BJR has received consulting or advisory fees from Deep6AI, AstraZeneca, and Tesaro, a GSK company; DMC declares advisory/consultancy for AstraZeneca, GSK, Clovis Oncology; speaker bureaus for AstraZeneca, GSK; and travel/accommodation/expenses from AstraZeneca, GSK; JP is an employee of GSK and holds stock/shares at GSK and Boston Scientific; AKG, JAH, and LK are employees of GSK; AAG is a former GSK employee; EXD, TW, and JS are employees of Analysis Group, which received consulting fees from GSK; RS reports honoraria from Arcus, Clovis, Genentech, GSK, Immunogen, Instil Bio, Merck, and Seagen; and advisory fees from Genentech; BJM reports consulting fees from Amgen, Aravive AstraZeneca, Clovis, GOG Foundation, Gradalis ImmunoGen Laekna Health Care, Merck, Mersana Myriad, Nucana Oncomed Oncoquest Pfizer, Roche/Genentech, GSK), speakers’ bureau fees (Clovis, Merck, Roche/Genentech, GSK), honoraria (Amgen, Aravive AstraZeneca, Clovis, GOG Foundation, Gradalis ImmunoGen Laekna Health Care, Merck, Mersana Myriad, Nucana Oncomed Oncoquest Pfizer, Roche/Genentech, GSK)., (© 2024 GSK.)

Introduction: We evaluated real-world outcomes in patients with advanced ovarian cancer (AOC) based on their cumulative risk profile and maintenance therapy (MT) status following first-line (1L) treatment., Methods: This retrospective observational study of a nationwide electronic health record-derived de-identified database included adult patients diagnosed with stage III/IV OC from January 1, 2011 to February 28, 2021, who received 1L therapy and had ≥ 12 weeks of follow-up after the index date (end of 1L therapy). Patients were grouped according to whether they received MT or active surveillance (AS) following 1L treatment and by the cumulative number of risk factors (RF) present (stage IV disease; no surgery/treated with neoadjuvant therapy and interval debulking surgery; had postoperative visible residual disease; and had BRCA wild-type disease/unknown BRCA status). Time to next treatment (TTNT) and overall survival (OS) were assessed with a cloning and inverse probability of censoring (IPC)-weighted Kaplan-Meier method., Results: Among 1920 patients, 22.2% received MT and 77.8% received AS. Median IPC-weighted TTNT and OS were 13.3 months (95% CI 11.7-15.8) and 39.1 months (95% CI 32.5-48.6) in the MT cohort, respectively, and 8.6 months (95% CI 8.0-9.5) and 38.4 months (95% CI 36.4-41.0) in the AS cohort, respectively. Almost all patients had ≥ 1 RF (MT 95.3%; AS 96.7%). Median IPC-weighted TTNT was shorter among patients with more RF in both cohorts (MT: 1 RF, 19.3 months, 95% CI 13.5-37.8; 2 RF, 17.2 months, 95% CI 12.8-20.2; 3 RF, 11.0 months, 95% CI 8.2-13.8; 4 RF, 7.0 months, 95% CI 6.2-8.8; AS: 1 RF, 17.7 months, 95% CI 13.5-22.3; 2 RF, 10.2 months, 95% CI 9.1-11.5; 3 RF, 6.5 months, 95% CI 5.8-7.4; 4 RF, 4.1 months, 95% CI 3.5-4.5)., Conclusion: Regardless of RF number, MT was associated with longer TTNT in real-world patients with AOC., (© 2023. The Author(s).)

Purpose: To identify risk factors for disease progression or death and assess outcomes by risk categories in real-world patients with advanced ovarian cancer., Methods: This retrospective study included adult patients from a nationwide electronic health record-derived deidentified database with stage III/IV ovarian cancer who received first-line therapy and had ≥12 weeks of follow-up after index date (end of first-line therapy). Factors predictive of time to next treatment and overall survival (OS) were assessed. Patients were grouped according to the cumulative number of high-risk factors present (stage IV disease, no debulking surgery or neoadjuvant therapy and interval debulking surgery, visible residual disease after surgery, and breast cancer gene [ BRCA ] wild-type disease/unknown BRCA status), and time to next treatment and OS were assessed., Results: Region of residence, disease stage, histology, BRCA status, surgery modality, and visible residual disease were significant predictors of time to next treatment; age, Eastern Cooperative Oncology Group performance status, disease stage, BRCA status, surgery modality, visible residual disease, and platelet levels were significant predictors of OS (N = 1,920). Overall, 96.4%, 74.1%, and 40.3% of patients had at least 1, 2, or 3 high-risk factors, respectively; 15.7% of patients had all four high-risk factors. Observed median time to next treatment was 26.4 months (95% CI, 17.1 to 49.2) in patients with no high-risk factors and 4.6 months (95% CI, 4.1 to 5.7) in patients with four high-risk factors. Observed median OS was shorter among patients with more high-risk factors., Conclusion: These results underscore the complexity of risk assessment and demonstrate the importance of assessing a patient's cumulative risk profile rather than the impact of individual high-risk factors. They also highlight the potential for bias in cross-trial comparisons of median progression-free survival because of differences in risk-factor distribution among patient populations.

Objective: To determine whether gastrointestinal (GI) disorder insurance claims in the year preceding a diagnosis of ovarian cancer (OC) lead to differing treatment allocations. The hypothesis is that GI disorders may be indicative of advanced OC., Methods: This retrospective study identified patients with newly diagnosed OC from January 2015 to January 2019 in the IBM® MarketScan® US commercial insurance and Medicare databases. Analysis was limited to patients with primary or interval debulking surgery or chemotherapy, with or without GI claims in the year prior to diagnosis, with commercial or Medicare coverage for ≥12 months prior and ≥1 month after the index date. Patients were compared in terms of the odds of treatment with neoadjuvant chemotherapy (NCT) or primary debulking surgery (PDS) (logistic regression analysis). Median treatment-free interval in the subset of patients with antineoplastic treatment was compared (Kaplan-Meier analysis)., Results: Of the 6286 patients, 22% had a diagnosis of ≥1 GI disorder before their OC diagnosis. Of these patients, 39% were diagnosed with a GI disorder between 6 and 12 months before OC diagnosis and 61% were diagnosed <6 months prior. Women with a GI diagnosis were more likely to undergo NCT than PDS (odds ratio [OR], 1.37; P < 0.0001); this remained significant even when controlling for age, region, insurance plan type, and index year (OR, 1.24; P = 0.001)., Conclusions: In this database, ≈25% of women with OC had a GI claim within the past year and were more likely treated with NCT, an indicator of more advanced disease with a worse prognosis. This suggests that OC should be considered in the differential diagnosis among women with GI complaints, which could alter treatment allocation., Competing Interests: Declaration of Competing Interest DMC reports personal fees from GlaxoSmithKline; JN has no conflicts to report; JP reports employment with GlaxoSmithKline; BJM reports grants and personal fees from GlaxoSmithKline., (Copyright © 2021. Published by Elsevier Inc.)