OBJECTIVE: The phase IIIb OPINION trial (NCT03402841) investigated olaparib maintenance monotherapy in patients without a deleterious or suspected deleterious germline BRCA1/BRCA2 mutation (gBRCAm) who had platinum-sensitive relapsed ovarian cancer (PSROC) and had received ≥2 previous lines of platinum-based chemotherapy. METHODS: In this single-arm, open-label, international study, patients who had responded to platinum-based chemotherapy received maintenance olaparib tablets (300 mg twice daily) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS) (modified RECIST version 1.1). A key secondary endpoint was PFS by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. The primary analysis of PFS was planned for 18 months after the last patient received their first dose. RESULTS: Two hundred and seventy-nine patients were enrolled and received olaparib. At data cutoff (October 2, 2020), 210 PFS events had occurred (75.3% maturity) and median PFS was 9.2 months (95% confidence interval [CI], 7.6-10.9) in the overall population. At 12 and 18 months, 38.5% and 24.3% of patients were progression-free, respectively. In the predefined biomarker subgroups, median PFS was 16.4, 11.1, 9.7, and 7.3 months in sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative patients, respectively. The most common treatment-emergent adverse events (TEAEs) were nausea (48.4%) and fatigue/asthenia (44.1%). TEAEs led to dose interruption, dose reduction, and treatment discontinuation in 47.0%, 22.6%, and 7.5% of patients, respectively. CONCLUSION: Maintenance olaparib demonstrated clinical benefit in patients without a gBRCAm, and across all subgroups, compared with historical placebo controls. There were no new safety signals.

AstraZeneca Cambridge UK

General University Hospital Prague 1st Faculty of Medicine Charles University Prague Czech Republic

Hospital Universitario Reina Sofía Córdoba Spain

Initia Oncology Valencia Spain

Institute of Oncology Ljubljana Ljubljana Slovenia

Medical University Karol Marcinkowski Poznań Poland

Olsztyn Provincial Specialist Hospital Olsztyn Poland

Oslo University Hospital Institute of Clinical Medicine University of Oslo Oslo Norway

Ottawa Hospital Research Institute Ottawa ON Canada

Princess Margaret Hospital Department of Medical Oncology Toronto ON Canada

Program in Solid Tumors Center for Applied Medical Research and Clinica Universidad de Navarra Madrid Spain

Skåne University Hospital Lund University Lund Sweden

UCL Cancer Institute University College London and UCL Hospitals London UK

University of Milan Bicocca and European Institute of Oncology IRCCS Milan Italy

Vall d'Hebron Institute of Oncology Hospital Universitari Vall d'Hebron Vall d'Hebron Barcelona Hospital Campus Barcelona Spain

Citace poskytuje Crossref.org

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ClinicalTrials.gov
NCT03402841