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Objective: The aim of the present analysis was to explore the efficacy of Bevacizumab (Bev) on survival outcome in advanced low grade serous ovarian cancer (LGSOC) both in first line and in recurrent setting., Methods: In retrospective observational multicenter study, we described the outcome of LGSOC patients enrolled in the MITO 22 study and treated with chemotherapy (CT) with or without Bev. Patients receiving Bev in first-line or in recurrence were considered and compared with patients receiving CT alone (stage III and IV in first line; platinum based-CT in second line). Descriptive and survival analyses were performed for each group., Results: Out of 128 patients included in MITO 22, 46 LGSOC patients receiving Bev in first line setting or at the time of first recurrence were identified. In first line, 30 patients received Bev + CT and 65 CT alone and the median PFS were 47.86 months (95% CI: 31.48 - NR) and 22.63 months (95% CI 15-39.24) (p-value 0.0392), respectively. In the recurrent setting, 16 patients who received Bev + CT were compared to 33 women treated with platinum-based CT alone. Median PFS were 37.1 months (95% CI: 13.42-40.56) and 11.22 months (95% CI: 8.26-15.63) (p-value 0.013), respectively., Conclusions: Our study suggests that Bev might be effective in LGSOC both at diagnosis and at the time of relapse. These data warrants further studies., Competing Interests: Declaration of Competing Interest CM reports consultant/advisory board for Clovis, Pharmamar, GSK, Astrazeneca, Arquer diagnostic and travel accommodation from Pharmamar and Roche. VS reports honoraria from GSK, PharmaMar, Roche, MSD, EISAI, Clovis, Oncology, AstraZeneca. FR reports honoraria from GSK, Pharmamar, Clovis, MSD and Roche. FP reports honoraria for educational and advisory activity from Incyte, GSK, Eli Lilly, Ipsen, Astellas, AstraZeneca, Roche, BMS, Bayer, Clovis, Pierre Fabre and grants for clinical trials to his institution from Roche, Astra Zeneca, Pfizer, MSD, Bayer, Incyte Taiho, Janssen, Exelixis, Ailenor, Daiichi Sankyo. AF reports relationship with commercial interests with AstraZeneca, MSD, Johnson & Johnson and Pharmamar. DL reports research funding from Clovis, GSK and MSD, personal interests with AstraZeneca, Clovis Oncology, GSK, Pharmamar, MSD and financial interests with Clovis, Genmab, GSK, MSD. Board of Directors, GCIG (Gynecologic Cancer Inter Group). GS reports research support from MSD and honoraria from Clovis Oncology. Consultant for Tesaro and Johnson & Johnson. SP reports honoraria from AstraZeneca, MSD, Roche, Pfizer, Clovis, GSK, Pharmamar and research funding from MSD, Roche, Astrazeneca and Pfizer. LM, MT, LA, MB, DC, VT, GC, VL, CP, GV, SCC, JV have nothing to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published., Methods: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®)., Results: A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found., Conclusions: MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics., Clinical Trial Registration: This study is registered under NCT02408536 on ClinicalTrials.gov ., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinical trials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity and efficacy of these agents and explore differences in clinical outcomes related to RAS/RAF mutational status., Methods: In March 2022, we searched Pubmed, Web of Science, Scopus, and the major conference proceedings (ASCO, ESMO) for randomized and non-randomized clinical trials evaluating MEKi as single agent in recurrent LGSC. The screening was performed independently by two reviewers. Objective response rate (ORR) and progression-free survival (PFS) data were extracted, and RevMan 5.3 software was used for statistical analysis., Results: A total of 4 clinical trials involving 648 patients were included. In the intention-to-treat population, use of a MEK inhibitor was not associated with a significant improvement in PFS, with a pooled Hazard Ratio equal to 0.75 (95 % CI: 0.30 - 1.86, P = 0.54). Heterogeneity was significant (I 2  = 92 %; P = 0.0004). In the overall study population, the pooled odds ratio of ORR for MEKis compared to control treatment was 2.61 (95 % CI: 0.65 - 10.54, P = 0.18). Specifically, ORR was 20.12 % in patients treated with MEKis compared to 9.09 % in women receiving standard treatment. Heterogeneity was significant (I 2  = 85 %; P = 0.009)., Conclusions: Although no statistically significant improvement in PFS was demonstrated, the available data show clear signals of activity, at least for some MEKis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Platinum-resistant ovarian cancer patients have a poor prognosis and few treatment options are available. Preclinical and clinical data demonstrated that the combination of poly-ADP ribose polymerase inhibitors with immune checkpoint inhibitors could have a synergistic antitumor activity in this setting of patients., Primary Objective: The primary objective is to assess the efficacy of niraparib plus dostarlimab compared with chemotherapy in recurrent ovarian cancer patients not suitable for platinum treatment., Study Hypothesis: This trial will assess the hypothesis that niraparib plus dostarlimab therapy is effective to increase overall survival, progression-free survival, and time to first subsequent therapy respect to chemotherapy alone, with an acceptable toxicity profile., Trial Design: This is a phase III, multicenter trial, where recurrent ovarian cancer patients not eligible for platinum re-treatment will be randomized 1:1 to receive niraparib plus dostarlimab vs physician's choice chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent. The study will be performed according to European Network for Gynaecological Oncological Trial groups (ENGOT) model B and patients will be recruited from 40 sites across MITO, CEEGOG, GINECO, HeCOG, MANGO, and NOGGO groups., Major Inclusion/exclusion Criteria: Eligible patients must have recurrent epithelial ovarian cancer not eligible for platinum retreatment. Patients who received previous treatment with poly-ADP ribose polymerase inhibitors and/or immune checkpoint inhibitors will be eligible. No more than two prior lines of treatment are allowed., Primary Endpoint: The primary endpoint is overall survival defined as the time from the randomization to the date of death by any cause., Sample Size: 427 patients will be randomized., Estimated Dates for Completing Accrual and Presenting Results: June 2024 TRIAL REGISTRATION NUMBER: NCT04679064., Competing Interests: Competing interests: VS reports personal financial interest with Roche, Pharmamar, Astrazeneca, MSD, Clovis, Tesaro, GSK, and EISAI. SP reports honoraria from GSK, Roche, AstraZeneca, MSD, Clovis, and Pharmamar. EB reports funded research from EU, BMBF, AstraZeneca, Roche Diagnostics, Bayer, and MSD, honoraria/travels from Roche, Amgen, MSD, Clovis, AstraZeneca, Tesaro, GSK, and Roche Diagnostics, consulting/advisory board for Amgen, AstraZeneca, Clovis, Eisai, GSK, MSD, Tesaro, Roche, and Seattle Genetics. DC has been part of the advisory board of Roche, AstraZeneca, Merck, GSK, and Sotio. NC reports personal financial interest with Pharmamar, AstraZeneca, Roche, MSD/Merck, Clovis Oncology, Tesaro/GSK, Novartis, Pfizer, Takeda, Biocad, Immonogen, Mersana, and EISAI, and institutional financial interests (Research Grants) with AstraZeneca, Pharmamar, and Roche. JSF has been part of the advisory board of Novartis, Pfizer, AstraZeneca, Lilly, Roche, Biocad, Daiichi, Tesaro, GSK, and Pierre Fabre. FZ reports honoraria for lectures and advisory role for AstraZeneca, Daiichi, Eli-Lilly, Merck, Novartis, and Pfizer. GS reports Grant/Research Support by MSD and consultant for Tesaro, Johnson & Johnson, and AstraZeneca. DL reports personal financial interests (advisory roles) with AstraZeneca, Clovis Oncology, Merck, Roche, Tesaro-GSK, Amgen, and Pharmamar, and institutional financial interests (Study Grants) with Tesaro/GSK, Merck, Roche, Pharmamar, and Clovis. Board of Directors, and GCIG (Gynecologic Cancer Inter Group)., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)