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.

Department of Gynecologic Oncology Medical University Karol Marcinkowski Poznań Poland

Department of Gynecology National Institute of Cancer Budapest Hungary

Department of Medical Oncology ICO l'Hospitalet Hospital Duran i Reynals IDIBELL L'Hospitalet de Llobregat Barcelona Spain

Department of Medical Oncology The Christie NHS Foundation Trust and University of Manchester Manchester UK

Department of Medicine and Surgery University of Milan Bicocca and European Institute of Oncology IRCCS Milan Italy

Department of Obstetrics and Gynaecology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Obstetrics and Gynecology University Hospital Ostrava and University of Ostrava Ostrava Poruba Czech Republic

Department of Oncology Cancer Centre Guy's and St Thomas' NHS Foundation Trust London UK

Department of Oncology University of Turin at Mauriziano Hospital Turin Italy

Department of Urology and Gynecology Istituto Nazionale Tumori 'Fondazione G Pascale' IRCCS Napoli Italy

Division of Medical Oncology and Hematology Princess Margaret Cancer Centre Toronto ON Canada

Global Medical Affairs AstraZeneca Cambridge UK

GMA Payer Biometrics Oncology R and D AstraZeneca Cambridge UK

Leeds Institute of Medical Research St James's University Hospital Leeds UK

Medical Oncology Clinic MHAT Central Onco Hospital OOD Plovdiv Bulgaria

Medical Oncology Clinic MHAT for Women's Health Nadezhda OOD Sofia Bulgaria

Medical Oncology Department Beatson West of Scotland Cancer Centre and University of Glasgow Glasgow UK

Medical Oncology Department ICO Badalona Hospital Universitari Germans Trias i Pujol Badalona Spain

Servico de Oncología Médica Hospital Universitario Miguel Servet Zaragoza Spain

Translational Medicine Oncology R and D AstraZeneca Cambridge UK

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