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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.)

Background: PARP inhibitors (PARPi) have revolutionized the management of high-grade epithelial ovarian cancer (HGOC) treatment. However, a significant number of patients relapse or progress under PARPi, leading to the introduction of a new line of systemic therapy such as chemotherapy. In patients with a limited number of metastatic sites at progression, -referred to as an oligometastatic progression- a potential indication for local therapy followed by re-introduction or continuation of PARPi treatment rather than initiating a new line of chemotherapy could be proposed. However, the impact of such strategies on progression free survival (PFS) in these patients remains unknown., Methods: This international multicenter retrospective study evaluated the efficacy of PARPi continuation or re-introduction in patients with HGOC after local treatment for oligometastatic progression. The main objective was to assess PFS under PARPi after local therapy (PFS post-LT). Secondary objectives included safety and overall survival (OS)., Results: 74 patients were identified in 20 centers between April 2020 and November 2021. 65% of patients were BRCA mutated and 92% had received ≥2 lines of prior systemic chemotherapy before the initial introduction of PARPi. Main progression sites were lymph nodes (42%), peritoneum (27%), liver (16%), other visceral (16%) and abdominal wall (4%). Local therapies included radiotherapy (45%), surgery (43%), both (7%), percutaneous thermal ablation (4%) or chemoembolization (1%). Median PFS post-LT was 11.5 months [95% CI 7.4; 17.2]. After a median follow up of 14.8 months, 6 patients (8.1%) discontinued PARPi due to toxicity. The 1-year overall survival rate was 90.7% [95% CI 79.1; 96.0]., Conclusions: With close to one year without progression or introduction of a new line of systemic therapy, this study reports the feasibility and potential benefit of this original strategy in patients with oligometastatic progression under PARPi., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Prognostic significance of endometrioid epithelial ovarian cancer (EOC) is controversial. We compared clinical, pathological, and biological features of patients with endometrioid and serous EOC, and assessed the independent effect of histology on outcomes., Methods: We conducted a multicenter retrospective analysis of patients with EOC selected from the French Epidemiological Strategy and Medical Economics OC database between 2011 and 2016. Our main objective was to compare overall survival (OS) in endometrioid and serous tumors of all grades. Our second objectives were progression-free survival (PFS) and prognostic features., Results: Out of 10,263 patients included, 3180 cases with a confirmed diagnosis of serous (N = 2854) or endometrioid (N = 326) EOC were selected. Patients with endometrioid histology were younger, more often diagnosed at an early stage, with lower-grade tumors, more frequently dMMR/MSI-high, and presented more personal/familial histories of Lynch syndrome-associated cancers. BRCA1/2 mutations were more frequently identified in the serous population. Endometrioid patients were less likely to receive chemotherapy, with less bevacizumab. After median follow-up of 51.7 months (95CI[50.1-53.6]), five-year OS rate was 81% (95CI[74-85]) in the endometrioid subgroup vs. 55% (95CI[53-57] in the serous subset (p < 0.001, log-rank test). In multivariate analyses including [age, ECOG-PS, FIGO, grade, and histology], the endometrioid subtype was independently associated with better OS (HR = 0.38, 95CI[0.20-0.70], p= 0.002) and PFS (HR = 0.53, 95CI[0.37-0.75], p < 0.001)., Conclusions: Clinicopathological features at diagnosis are not the same for endometrioid and serous EOC. Endometrioid histology is an independent prognosis factor in EOC. These observations suggest the endometrioid population requires dedicated clinical trials and management., Competing Interests: Declaration of Competing Interest All the authors declare that they have no conflicts of interest to disclose related to this work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: A nationwide cervical cancer (CC) screening program was implemented in France in 2018. Asymptomatic women are invited for a cytological test once every 3 years (age, 25-29 years), and an HPV test every 5 years (age, 30-65 years). We investigated the characteristics of women who are resistant to CC screening., Methods: Since 2005, the EDIFICE survey program has assessed attitudes toward cancer screening in France. The 6th edition (2017) included 12,046 representative women (age, 18-69 years). Social vulnerability was assessed using the EPICES score. Multivariate stepwise logistic regression analysis identified factors correlated with nonuptake of CC screening., Results: Questionnaires from 4499 women (age, 25-65 years) with no history of cancer were analyzed; 88% (N = 3960) reported at least one test in their lifetime, and 73% (N = 3262) did the test in the previous 3 years. Compared to ever-screened women, never-screened women were younger (38 ± 11 yrs. vs 44 ± 12 yrs., P < 0.05), and more likely to be single (48% vs 20%, P < 0.05) and/or socially vulnerable (59% vs 38%, P < 0.05). In multivariate analysis, items significantly (P < 0.05) associated with never screening included living alone (OR = 2.26, 95% CI [1.85-2.75]) and social vulnerability (OR = 1.95 [1.59-2.40]). Women who were not compliant with recommendations were more likely to be older (mean age, 49.2 yrs. vs. 43.2 yrs), living alone (single, widowed or divorced, 40% vs. 30%, P < 0.05), and/or socially vulnerable (55% vs. 35%, P < 0.05; OR = 1.78, 95% CI [1.49-2.12])., Conclusion: This analysis identified several factors associated with never screening and under-screening. Effective prevention messages should specifically target these populations., Competing Interests: Declaration of Competing Interest Thibault de la Motte Rouge, Morgan Rouprêt and Jean-François Morère have received honoraria from Roche. Christine Lhomel is an employee of Roche. The other authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients., Patients and Methods: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients., Results: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival., Conclusion: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The French national rare gynecological tumor network has been established to improve the quality of care through offering expertise in double reading histological diagnosis, reviewing cases and guiding management of these tumors through specialized multidisciplinary tumor boards and online clinical guidelines (www.ovaire-rare.com). The aim of this study is to evaluate the impact of the development and implementation of this network by assessing the conformity of medical practice with the guidelines concerning the granulosa cell tumors (GCTs)., Methods: This is a French nationwide study, including 463 patients (out of the 639 identified patients) with a definitive diagnosis of GCT between 2011 and 2016. Surgical practices were analyzed for conformity with the current guidelines (www.ovaire-rare.org). Medical records, surgical and pathological reports were systematically analyzed. Total conformity was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysterectomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsies and peritoneal cytology) according to the FIGO stage. Partial conformity referred to a conservative or radical surgery without surgical staging and non-conformity was defined as a non-optimal surgery as recommended by the guidelines., Results: Median age at diagnosis was 49 years old (range 10-89). The median size of tumor was 94 mm (range 5-400). Radical surgery was performed in 240 patients (52%); while a fertility-sparing surgery was performed in 98 cases (21%). A surgical staging was performed in 76 cases (16%) and an evaluation of the endometrium in 289 cases (62%). Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (30%) and not assessable in 48 cases (10%). A statistically significant difference for compliance was observed in restaging surgery (p < 0,001), radical surgery (p = 0,017) and the period (before or after) of the implementation of the network (p < 0,001). Survival analyses did not allow us to demonstrate a significant difference in overall survival nor in PFS although there was a trend in favor of optimal surgery compared to incomplete/non optimal surgery., Conclusion: Surgical management's conformity to the guidelines increases over time from 2011 to 2016. According to this study, the implementation of a national network dedicated to rare gynecologic tumors seems to significantly improve the surgical management of the patients with ovarian granulosa cell tumors., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice., Methods: Multicenter (8 hospitals) European retrospective study of relapsing EOC patients having germline or somatic mutations of BRCA1/BRCA2 genes and treated with olaparib as maintenance therapy after platinum-based chemotherapy., Results: One hundred and fifteen patients were included. Median age was 54 years. There were 90 BRCA1 carriers, 24 BRCA2 carriers and one patient had germline mutation of BRCA1 and BRCA2. Six patients had somatic mutations (all BRCA1) and 109 had germline mutations. Ninety percent had serous carcinomas and were platinum-sensitive. Following ultimate platinum-based chemotherapy, 69% of the patients had normalization of CA-125 levels and 87% had RECIST objective responses, either partial (53%) or complete (34%). After a median follow-up of 21 months, median PFS was 12.7 months and median OS was 35.4 months. In multivariate analysis, factors associated with prolonged PFS under olaparib were: platinum-free interval (PFI) ≥ 12 months, RECIST complete response (CR) or partial response (PR) and normalization of CA-125 upon ultimate platinum-based chemotherapy. Factors associated with prolonged OS were PFI ≥ 12 months, CR and normalization of CA-125., Conclusions: Platinum-free interval ≥ 12 months, complete response and normalized CA-125 levels after ultimate platinum-based chemotherapy are associated with prolonged PFS and OS in relapsing BRCA1/BRCA2 mutated ovarian cancer patients who received olaparib as maintenance therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact., Methods: This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively., Results: Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS., Conclusions: An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs., Conflict of Interest Statement: No conflict of interest., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To evaluate the different kinetic parameters of serum CA125 during neoadjuvant chemotherapy (NAC) to predict optimal interval debulking surgery (IDS)., Methods: The present retrospective multicenter study included patients with advanced ovarian cancer treated with neoadjuvant platinum-based chemotherapy followed by IDS between 2002 and 2009. Demographic data, CA125 levels, radiographic data, chemotherapy and surgical-pathologic information were obtained. Univariate and multivariate analyses were performed to evaluate variables associated with complete IDS. ROC analysis was used to determine potential cut-off values to predict the likelihood of complete cytoreduction via IDS., Results: One hundred and forty-eight patients met the study criteria. Ninety-three patients (62.8%) had optimal cytoreduction with no residual macroscopic disease (CC-0) after IDS. In multivariate analyses, the CA125 level after the 3rd NAC was an independent predictor for optimal cytoreduction (odds ratio: 0.98 [0.97-0.99], p=0.04). The area under the ROC curve was 0.73. A threshold of 75 UI/ml displayed the most predictive power. The odds ratio to predict complete cytoreduction was 3.29 [1.56-7.10] (p=0.0008)., Conclusion: Our data indicate that for advanced ovarian cancer, a CA125 level less than 75 UI/ml after the 3rd NAC was an independent predictor factor for complete IDS., (Copyright © 2014 Elsevier Inc. All rights reserved.)