Phase 3b OPINION Primary Analysis of Olaparib Maintenance Monotherapy for Nongermline BRCA1/2-Mutated Platinum-Sensitive Relapsed Ovarian Cancer

Results of the primary analysis of the phase 3b OPINION study supported the use of olaparib maintenance therapy in patients with nongermline BRCA1/2-mutated platinum-sensitive relapsed ovarian cancer.

The phase 3b, single-arm, OPINION study (NCT03402841) investigated olaparib maintenance monotherapy in patients with nongermline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer. The results of this study were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

Key eligibility criteria were relapsed high-grade serous or endometrioid ovarian cancer harboring non-gBRCAm, ≥2 previous lines of platinum-based chemotherapy, and complete response or partial response to last platinum-based chemotherapy. Eligible patients received maintenance olaparib (300 mg orally, twice a day) until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included PFS by homologous recombination deficiency (HRD) and somatic BRCA mutation (sBRCAm) status, as assessed by central Myriad tumor and germline testing; time to first subsequent treatment; time to treatment discontinuation or death; overall survival; safety; and tolerability. Primary analysis was planned 18 months after the last patient was enrolled; the data cutoff date was October 2, 2020.

A total of 279 patients were enrolled in the study. The mean age of the study population was 64 years; the majority (90.7%) had confirmed non-gBRCAm. In the overall study population, the median PFS was 9.2 months; the 12-month PFS rate was 38.5%, and the 18-month PFS rate was 24.3%. The PFS benefit extended to key subgroups evaluated, including those tested by Myriad HRD/BRCAm status (HRD-positive including sBRCAm: 11.1 months; HRD-positive excluding sBRCAm: 9.7 months; sBRCAm: 16.4 months). Median time to first subsequent treatment was 13.9 months.

Treatment-emergent adverse events (TEAEs) were consistent with the known safety profile of olaparib. Grade ≥3 TEAEs occurred in 29.0% of patients, and serious TEAEs occurred in 19.7% of patients. TEAEs led to dose interruption in 47.0% of patients, dose reduction in 22.6% of patients, and treatment discontinuation in 7.5% of patients.

Primary analysis results of the OPINION study support the use of olaparib maintenance therapy in patients with non-gBRCAm platinum-sensitive relapsed ovarian cancer.

Source: Poveda A, Lheureux S, Colombo N, et al. Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): phase IIIb OPINION primary analysis. J Clin Oncol. 2021;39(suppl_15). Abstract 5545.