Olaparib (tablet formulation) is approved in the US for maintenance treatment of PSROC based on 2 pivotal studies (Study 19 [NCT00753545], SOLO2 [NCT01874353]), which showed a significant progression free survival (PFS) benefit. In Study 19, clinical benefit was observed in pts with or without BRCA mutations, supporting the hypothesis that platinum sensitivity is a surrogate marker for homologous recombination deficiency (HRD). This study was designed to further prospectively explore olaparib activity in non-gBRCAm pts.
This single-arm, open-label, multicenter, phase 3b study (OPINION; NCT03402841) was designed to assess the efficacy and safety of olaparib maintenance therapy in women with non-gBRCAm, high-grade serous or endometrioid PSROC. Eligible pts (≥18 y, ECOG PS 0-1, ≥2 lines of prior platinum therapy [PT], and in response [CR/PR] to last PT) will be treated with olaparib 300 mg tablets twice daily until disease progression or unacceptable toxicity. Primary endpoint is investigator-assessed PFS (RECIST v1.1). Secondary endpoints are time to first subsequent therapy or death, time to treatment discontinuation or death, chemotherapy-free interval, PFS by tumor HRD status, and health-related quality of life (FACT-O). Safety and tolerability also will be assessed. Exploratory endpoints are overall survival, evaluating treatment impact and disease state on health state utility (EQ-5D-5L), and PFS in pts stratified by molecular subgroups (including mutations in HR repair genes, microsatellite instability status, TP53 mutation disruption status, and tumor mutation load score). Correlation between HRD status from tumor and circulating tumor DNA in matched pts also will be explored. A sample size of 250 pts was opted for adequate level of precision for PFS estimation, with mean 95% CI width at 30 mo after first pt is estimated at 3.27 mo from 500 simulations of a piecewise exponential model with median PFS of 8.5 mo at 12 mo enrollment. Efficacy analyses will be based on all enrolled pts and safety analyses on enrolled pts receiving ≥1 olaparib dose. Enrollment is ongoing.
Clinical trial identification
Legal entity responsible for the study
Editorial assistance, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Kaveri Sidhu, PhD, of Cactus Communications (Mumbai, India).
A.M. Poveda: Consulting or advisory role: Roche, AstraZeneca, Novartis, Immunogen, Tesaro, PharmaMar. R. Davidson, A. Milner: Employment: AstraZeneca. C. Blakeley: Employment: AstraZeneca, Worldwide Clinical Trials; Stock ownership: Pfizer.