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Overall survival with maintenance olaparib in platinum-sensitive relapsed ovarian cancer by somatic or germline BRCA and homologous recombination repair mutation status
Pignata, S. Oza, A. Hall, G. Pardo, B. Madry, R. Cibula, D. Klat, J. Montes, A. Glasspool, R. Colombo, N.
Pignata, S.
Oza, A.
Hall, G.
Pardo, B.
Madry, R.
Cibula, D.
Klat, J.
Montes, A.
Glasspool, R.
Colombo, N.
Abstract
BACKGROUND: The open-label, single-arm, multicentre ORZORA trial (NCT02476968) evaluated maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) with a germline (g) or somatic (s) BRCA1 and/or BRCA2 mutation (BRCAm) or a non-BRCA homologous recombination repair mutation (non-BRCA HRRm). METHODS: Patients were in response to platinum-based chemotherapy after ≥2 prior lines of treatment and underwent prospective central screening for tumour BRCA status, then central gBRCAm testing to determine sBRCAm or gBRCAm status. An exploratory cohort evaluated non-BRCA HRRm in 13 predefined genes. Patients received olaparib 400 mg (capsules) twice daily until investigator-assessed disease progression. Secondary endpoints included overall survival (OS) and safety. RESULTS: 177 patients received olaparib. At the final data cutoff (25 June 2021), median OS from study enrolment was 46.8 (95% confidence interval [CI] 37.9-54.4), 43.2 (31.7-NC [not calculated]), 47.4 (37.9-NC) and 44.9 (28.9-NC) months in the BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts, respectively. No new safety signals were identified. CONCLUSION: Maintenance olaparib showed consistent clinical activity in the BRCAm and sBRCAm cohorts; exploratory analysis suggested similar activity in the non-BRCA HRRm cohort. These findings highlight that patients with PSR OC, beyond those with gBRCAm, may benefit from maintenance olaparib.
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Date
2025
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Pignata S, Oza A, Hall G, Pardo B, Madry R, Cibula D, et al. Overall survival with maintenance olaparib in platinum-sensitive relapsed ovarian cancer by somatic or germline BRCA and homologous recombination repair mutation status. British journal of cancer. 2025 May;132(8):725-32. PubMed PMID: 40097725. Pubmed Central PMCID: PMC11997082 with the Declaration of Helsinki, Good Clinical Practice Guidelines and the AstraZeneca policy of bioethics ( https://www.astrazeneca.com/content/dam/az/PDF/2019/Bioethics%20Policy%20final.pdf ) was approved by the Ethics Committee of Istituto Nazionale Tumori ‘Fondazione G Pascale’ (Reference no. 25/15). All patients provided written informed consent. Competing interests: Sandro Pignata: Honoraria from AstraZeneca, Merck Sharp & Dohme (MSD), Roche, Pfizer, GlaxoSmithKline (GSK) and Clovis Pharma; and research funding from Roche, MSD, AstraZeneca and Pfizer. Amit Oza: Principal investigator of investigator-initiated studies with AstraZeneca; institutional grant funding from AstraZeneca; and steering committee member (non-compensated) for AstraZeneca, Clovis Oncology and GSK. Geoff Hall: Research funding from IQVIA. Beatriz Pardo: Research funding from AstraZeneca, GSK, Clovis and MSD. Radoslaw Madry: Advisory board participation for AstraZeneca, Roche and GSK; and personal fees from AstraZeneca, Roche and GSK. David Cibula: Advisory board participation for AstraZeneca, Roche, Genmab, SOTIO, Merck and GSK. Jaroslav Klat: Reports no disclosures. Ana Montes: Reports no disclosures. Rosalind Glasspool: Principal investigator for trials sponsored by AstraZeneca, Clovis, Tesaro, Immunogen, Pfizer and Lilly; research funding from Clovis, Boehringer Ingelheim and Lilly/Ignyta; institution research funding from Tesaro; institutional fees from Novartis; and personal fees from AstraZeneca, MSD, Clovis, Tesaro, GSK, Immunogen and SOTIO. Nicoletta Colombo: Personal fees from AstraZeneca, MSD, Roche, Tesaro, GSK, Clovis Oncology, PharmaMar, Pfizer, Amgen, Novartis, BIODCAD and Immunogen. Imre Pete: Reports no disclosures. Ana Herrero Ibáñez: Consulting/advisory board participation for GSK; speakers’ bureau participation for Clovis, GSK, MSD, PharmaMar; and research funding from AstraZeneca and Roche. Margarita Romeo: Institution research funding from AstraZeneca, GSK, Clovis and Pfizer; personal fees from MSD and GSK; and AstraZeneca employment (this author became an AstraZeneca employee in July 2024; her contributions to this manuscript were made while working at her previous institution). Rumyana Ilieva: Reports no disclosures. Constanta Timcheva: Principal investigator of clinical trials of AstraZeneca, Roche, Novartis, Pfizer and Merck; and member of advisory boards of Astellas, Servier and Novartis. Massimo Di Maio: Principal investigator of clinical trials of Roche, Merck, BeiGene, Novartis, Pfizer and Exelixis; member of advisory boards of AstraZeneca, Roche, Novartis, Pfizer, Eisai, Astellas, Janssen, Merck and Amgen; and institutional research funding from GSK/Tesaro. Zahid Bashir: AstraZeneca employment (at time of study); and stock ownership of Omniac Pharm Consult Ltd. Rosie Taylor: AstraZeneca employment and stock ownership. Alan Barnicle: AstraZeneca employment and stock ownership. Andrew Clamp: Research funding from AstraZeneca; and honoraria from AstraZeneca, Clovis Oncology, GSK/Tesaro and Eisai. Epub 2025/03/18. eng.