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Purpose: To evaluate atezolizumab combined with platinum-based chemotherapy (CT) followed by maintenance niraparib for late-relapsing recurrent ovarian cancer., Methods: The multicenter placebo-controlled double-blind randomized phase III ENGOT-OV41/GEICO 69-O/ANITA trial (ClinicalTrials.gov identifier: NCT03598270) enrolled patients with measurable high-grade serous, endometrioid, or undifferentiated recurrent ovarian cancer who had received one or two previous CT lines (most recent including platinum) and had a treatment-free interval since last platinum (TFIp) of >6 months. Patients were stratified by investigator-selected carboplatin doublet, TFIp, BRCA status, and PD-L1 status in de novo biopsy and randomly assigned 1:1 to receive either atezolizumab or placebo throughout standard therapy comprising six cycles of a carboplatin doublet followed (in patients with response/stable disease) by maintenance niraparib until progression. The primary end point was investigator-assessed progression-free survival (PFS) per RECIST v1.1., Results: Between November 2018 and January 2022, 417 patients were randomly assigned (15% BRCA- mutated, 36% PD-L1-positive, 66% TFIp >12 months, 11% previous poly [ADP-ribose] polymerase inhibitor after frontline CT, and 53% previous bevacizumab). Median follow-up was 28.6 months (95% CI, 26.6 to 30.5 months). Atezolizumab did not significantly improve PFS (hazard ratio, 0.89 [95% CI, 0.71 to 1.10]; P = .28). Median PFS was 11.2 months (95% CI, 10.1 to 12.1 months) with atezolizumab versus 10.1 months (95% CI, 9.2 to 11.2 months) with standard therapy. Subgroup analyses generally showed consistent results, including analyses by PD-L1 status. The objective response rate (ORR) was 45% (95% CI, 39 to 52) with atezolizumab and 43% (95% CI, 36 to 49) with standard therapy. The safety profile was as expected from previous experience of these drugs., Conclusion: Combining atezolizumab with CT and maintenance niraparib for late-relapsing recurrent ovarian cancer did not significantly improve PFS or the ORR.

Background: Trabectedin in combination with pegylated liposomal doxorubicin (PLD) is approved for the treatment of patients with platinum-sensitive relapsed ovarian cancer. Nevertheless, there is currently limited information regarding this treatment in elderly patients with ovarian cancer in a real-world setting., Methods: This observational and multicentric study retrospectively evaluated trabectedin plus PLD in a real-world setting treatment of elderly patients diagnosed with platinum-sensitive relapsed ovarian cancer, treated according to the Summary of Product Characteristics (SmPC) from 15 GEICO-associated hospitals. Patients ≥ 70 years old at the time of treatment initiation and platinum-free intervals ≥ 6 months were considered eligible., Results: Forty-three patients with a median age of 74.0 years were treated between January 1st, 2015, and December 31st, 2019 in 15 Spanish centers. Four patients achieved complete response (9.3%), 14 (32.6%) partial response, and 13 (30.2%) stable disease as the best radiological response. In the analysis of biological overall response according to CA125 serum levels (i.e., Rustin criteria), 14 responded to the treatment (32.6%), 11 responded and normalized (25.6%), three patients stabilized (7.0%) and three progressed (7.0%). Median progression-free survival (PFS) and overall survival (OS) in the study population were 7.7 and 19.5 months, respectively. The most common grade 3/4 adverse events were neutropenia (n = 8, 18.7%) and asthenia (n = 5, 11.6%)., Conclusions: This analysis demonstrated that trabectedin combined with PLD is a feasible and effective treatment in elderly patients with platinum-sensitive relapsed ovarian cancer, showing an acceptable safety profile, which is crucial in the palliative treatment of these patients., (© 2024. The Author(s).)

Background: The GOG240 trial established bevacizumab with chemotherapy as standard first-line therapy for metastatic or recurrent cervical cancer. In the BEATcc trial (ENGOT-Cx10-GEICO 68-C-JGOG1084-GOG-3030), we aimed to evaluate the addition of an immune checkpoint inhibitor to this standard backbone., Methods: In this investigator-initiated, randomised, open-label, phase 3 trial, patients from 92 sites in Europe, Japan, and the USA with metastatic (stage IVB), persistent, or recurrent cervical cancer that was measurable, previously untreated, and not amenable to curative surgery or radiation were randomly assigned 1:1 to receive standard therapy (cisplatin 50 mg/m 2 or carboplatin area under the curve of 5, paclitaxel 175 mg/m 2 , and bevacizumab 15 mg/kg, all on day 1 of every 3-week cycle) with or without atezolizumab 1200 mg. Treatment was continued until disease progression, unacceptable toxicity, patient withdrawal, or death. Stratification factors were previous concomitant chemoradiation (yes vs no), histology (squamous cell carcinoma vs adenocarcinoma including adenosquamous carcinoma), and platinum backbone (cisplatin vs carboplatin). Dual primary endpoints were investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumours version 1.1 and overall survival analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03556839, and is ongoing., Findings: Between Oct 8, 2018, and Aug 20, 2021, 410 of 519 patients assessed for eligibility were enrolled. Median progression-free survival was 13·7 months (95% CI 12·3-16·6) with atezolizumab and 10·4 months (9·7-11·7) with standard therapy (hazard ratio [HR]=0·62 [95% CI 0·49-0·78]; p<0·0001); at the interim overall survival analysis, median overall survival was 32·1 months (95% CI 25·3-36·8) versus 22·8 months (20·3-28·0), respectively (HR 0·68 [95% CI 0·52-0·88]; p=0·0046). Grade 3 or worse adverse events occurred in 79% of patients in the experimental group and in 75% of patients in the standard group. Grade 1-2 diarrhoea, arthralgia, pyrexia, and rash were increased with atezolizumab., Interpretation: Adding atezolizumab to a standard bevacizumab plus platinum regimen for metastatic, persistent, or recurrent cervical cancer significantly improves progression-free and overall survival and should be considered as a new first-line therapy option., Funding: F Hoffmann-La Roche., Competing Interests: Declaration of interests AO reports personal fees for participation in the advisory boards of AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, MSD de España, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Shattuck Labs, iTeos, and Eisai; travel and accommodation support from AstraZeneca, PharmaMar, and Roche; and funding paid to institution from AbbVie Deutschland, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology, Eisai, F Hoffmann-La Roche, Regeneron Pharmaceuticals, Immunogen, MSD de España, Takeda, PharmaMar, Tesaro, and Bristol Myers Squibb. LG reports support for attending meetings or travel from Viatris, GSK, and MSD; consulting fees paid to institution for participation in the advisory boards of Clovis, GSK, AstraZeneca, and Seagen; and speaker honoraria paid to institution from AstraZeneca, GSK, and Eisai. JM-G reports personal fees for participation in the advisory boards of AstraZeneca, Clovis, GSK, and PharmaMar; research grants paid to institution from GSK and Roche; and travel and accommodation expenses from GSK−Tesaro, Pfizer, and PharmaMar. GV reports honoraria for speaker engagements from MSD, Pierre Fabre, GSK, and Pfizer; and consulting fees from Reveal Genomics. UDG reports personal consulting fees from Amgen, AstraZeneca, Pfizer, BMS, Clovis Oncology, Dompé Farmaceutici, Merck, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, Eisai, and Janssen; other funding paid to institution from AstraZeneca, Sanofi, and Roche; and support for attending meetings or travel from Pfizer, Ipsen, and AstraZeneca. KL reports personal honoraria from Eisai; participation on data safety monitoring or advisory boards of Eisai, MSD, Nykode, AstraZeneca, and GSK (honoraria paid to institution); and funding paid to institution from GSK. LW reports personal honoraria for participation in the advisory boards of AstraZeneca, Pfizer, GSK, Roche, MSD–Merck, Eisai, and Seagen; personal honoraria for speaker engagements from AstraZeneca, Eisai, GSK, Pfizer, Roche, MSD–Merck, and Seagen; and support for attending meetings or travel from GSK and MSD. NC reports consultancy or advisory roles for AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD−Merck, Nuvation Bio, OncXerna, Pfizer, Pieris, and Roche; promotional speaker roles for AstraZeneca, Novartis, Clovis Oncology, MSD−Merck, and GSK; research grants from AstraZeneca, GSK, and Roche; and support for attending meetings or travel from AstraZeneca and GSK. LD reports personal fees for scientific advisory boards from Aadi Bioscience and Regeneron; fees paid to institution for scientific advisory boards from Merck; membership of the British Journal of Obstetrics and Gynaecology Editorial Board; personal royalties for writing expert content for UpToDate, Wiley, and the American Society of Clinical Oncology; personal fees for continuing medical education activities for Advance Medical, CEA Group, and Clinical Care Options; research funding paid to institution for investigator-initiated trials from Merck; clinical trial grants paid to institution from Genentech−Roche, AbbVie (GOG 3005), Acrivon, Advaxis, Aduro BioTech, Alkermes, Blueprint, Constellation, Eisai, GSK–Novartis, Immunogen, Inovio, Iovance, Karyopharm, KSQ Therapeutics, Lycera, Merck, Morab, MorphoTek, Naveris, Nurix, OncoQuest, Pfizer, Syndax, Tesaro, and Zentalis; and fees paid to institution for membership of data and safety monitoring committees for Agenus and Inovio. AL reports personal fees for presentations or educational events from Medscape and PeerVoice; consulting fees paid to institution from Owkin; speaker honoraria paid to institution from MSD, GSK, AstraZeneca, and Eisai; fees paid to institution for participation in the advisory boards of AstraZeneca, MSD, Seagen, GSK, Genmab, Zentalis, and Blueprint; non-remunerated independent data safety monitoring board participation for Clovis and BMS; an educational grant paid to institution from AstraZeneca; and support for attending meetings or travel from OSE Immunotherapeutics. AG-O reports honoraria paid to institution for participation in the advisory board of Novartis; personal honoraria for speaker engagements from AstraZeneca, Pfizer, Novartis, and Lilly; and support for attending meetings or travel from Pfizer and Novartis. MJR reports personal fees for participation in the advisory boards of AstraZeneca, Clovis Oncology, GSK, PharmaMar, MSD de España, Eisai, and Roche; personal fees for speaker engagements from MSD, AstraZeneca, Clovis Oncology, GSK, and PharmaMar; and travel and accommodation from AstraZeneca, PharmaMar, Roche, GSK, and MSD de España. LF-M reports honoraria paid to institution for participation in the advisory boards of GSK; honoraria paid to institution for speaker engagements from GSK, AstraZeneca–MSD, and Eisai; and support for attending meetings or travel from AstraZeneca–MSD and GSK. DL reports personal fees for participation in the advisory boards of AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Oncoinvent, PharmaMar, Seagen, and Sutro; personal fees for consultancy roles from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, Novartis, PharmaMar, and Seagen; clinical trial or research funding to institution from Clovis Oncology, GSK, MSD, and PharmaMar; other financial or non-financial interests from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, Oncoinvent, PharmaMar, Roche, Seagen, and Sutro; and travel grants from AstraZeneca, Clovis Oncology, and GSK. IR-C reports personal honoraria for participation in the advisory boards of Adaptimmune, Agenus, Amgen, AstraZeneca, BMS, Clovis, Daiichi Sankyo, Deciphera, Eisai, EQRx, GSK, Merck Serono, MacroGenics, Mersana, Novartis, Onxeo, Roche, and Sutro Biopharma; honoraria paid to institution for participation in the advisory boards of MSD (translational research); and funding paid to institution for translational research from BMS. LM reports participation in the advisory board of Roche; and honoraria for speaker engagements from Roche, GSK, Clovis Oncology, AstraZeneca, Pfizer, Novartis, and Lilly. FJ reports honoraria for lectures, expert boards, and educational events from AstraZeneca, Clovis Oncology, GSK, and Seagen; travel and accommodation support from GSK, Eisai, and MSD; and financial support for national academic GINECO trials from GSK and AstraZeneca. JA reports honoraria for speaker bureaus from GSK, Roche, AstraZeneca, MSD, PharmaMar, and Clovis; and advisory boards for GSK, MSD, AstraZeneca, and Clovis. PF reports personal fees for expert testimony from Daiichi; personal fees for invited speaker engagements from GSK and MSD; and support for attending meetings or travel from Lilly, Novartis, and GSK. IR reports personal fees for advisory boards from AstraZeneca, Clovis Oncology, GSK, PharmaMar, Roche, and MSD; and travel and accommodation from AstraZeneca, PharmaMar, Roche, and GSK. CL reports honoraria for advisory board participation from GSK; personal honoraria for speaker engagements from GSK, Clovis Oncology, Eisai, and MSD; and support for attending meetings or travel from MSD and GSK. JAP-F reports honoraria for speaker engagements from AstraZeneca, PharmaMar, Pharma&, Clovis, and GSK; payment for expert testimony from AstraZeneca, GSK, Roche, and PharmaMar; support for attending meetings or travel from Karyopharm, AstraZeneca, Roche, and PharmaMar; grants paid to institution from GSK and PharmaMar; equipment, materials, drugs, medical writing, gifts, or other services paid to institution from GSK; participation on data safety monitoring or advisory boards for Ability Pharma; and has a patent pending in breast cancer. HD reports personal honoraria for advisory board participation from AstraZeneca. LMR reports honoraria for speaker engagements from Genmab−Seagen, Blueprint Oncology, Curio Science, and Physicians Education Resource; honoraria for participation in the advisory boards of AstraZeneca, Clovis Oncology, GOG Foundation, Aadi Biosciences, Seagen, OnTarget Laboratories, Merck, Mersana, Rubius Therapeutics, Myriad Genetics, Genentech−Roche, Eisai, Novocure, and Immunogen; consulting fees from the GOG Foundation; and funding paid to institution from Genentech−Roche, On Target Laboratories, Pfizer, Aivita Biomedical, Tesaro, AstraZeneca, Merck, Akeso Biopharma, and Grupo Español de Investigación en Cáncer ginecologico. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The aim of our study was to elucidate the impact of bevacizumab added to neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment and correlate the changes with the clinical outcome of the patients., Experimental Design: IHC and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 patients with ovarian cancer enrolled in GEICO 1205/NOVA clinical study before NACT and at the time of interval cytoreductive surgery., Results: Our results showed that the addition of bevacizumab to NACT plays a role mainly on lymphoid populations at the stromal compartment, detecting a significant decrease of CD4+ T cells, an increase of CD8+ T cells, and an upregulation in effector/regulatory cell ratio (CD8+/CD4+FOXP3+). None of the changes observed were detected in the intra-epithelial site in any arm (NACT or NACT-bevacizumab). No differences were found in myeloid lineage (macrophage-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significantly associated with progression-free survival (PFS)., Conclusions: The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at the cellular level, changes in CD4+, CD8+ lymphocyte populations, and CD8+/CD4+FOXP3 ratio have been detected only at the stromal site. On the basis of our results, we hypothesize about the existence of mechanisms of resistance that could prevent the trafficking of T-effector cells into the epithelial component of the tumor as a potential explanation for the lack of efficacy of ICI in the first-line treatment of advanced epithelial ovarian cancer. See related commentary by Soberanis Pina and Oza, p. 12., (©2023 The Authors; Published by the American Association for Cancer Research.)