Maintenance olaparib in patients (pts) with platinum-sensitive relapsed ovarian cancer (PSROC) by somatic (s) or germline (g) BRCA and other homologous recombination repair (HRR) gene mutation status: Overall survival (OS) results from the ORZORA study.

Abstract

5519 Background: In the SOLO2 (NCT01874353) trial, maintenance olaparib provided clinically meaningful improvement in OS for PSROC pts with a gBRCA mutation (m) compared with placebo (median 51.7 vs 38.8 months [mo], respectively). The ORZORA trial (NCT02476968) assessed efficacy and safety of maintenance olaparib in PSROC pts with a BRCAm (s or g) or a non-BRCA HRRm. Median progression-free survival (18.0 mo, BRCAm; 16.4, non-BRCA HRRm) was reported at primary data cutoff (DCO). We report final OS analyses. Methods: We conducted an open-label, single-arm, multicenter study of PSROC pts in response to platinum-based chemotherapy (PBC) after ≥2 prior lines of PBC. Pts underwent prospective central screening for tumor BRCAm status (myChoice CDx, Myriad Genetic Laboratories, Inc.), then central gBRCAm testing (BRACAnalysis CDx, Myriad Genetic Laboratories, Inc.) to determine s or g status. An exploratory cohort comprised of pts with predefined non-BRCA HRRm (FoundationOne CDx, Foundation Medicine, Inc.). Pts received maintenance olaparib (400 mg bid; capsules) until progression. OS and time to second progression (PFS2) were secondary endpoints. Results: 181 pts were enrolled (BRCAm n = 145 [s, n = 55; g, n = 87; s/g status unknown, n = 3]; non-BRCA HRRm, n = 33; unassigned, n = 3). At DCO (June 25, 2021), median OS follow-up in censored pts was 42.6 mo in BRCAm and 39.3 mo in non-BRCA HRRm pts. OS and PFS2 are reported in the Table. PBC was received as a subsequent therapy by 33.1% BRCAm, 32.7% sBRCAm, 33.3% gBRCAm, and 45.5% non-BRCA HRRm pts. 177 pts received ≥1 dose of olaparib and were included in safety analyses; 6.2% of pts discontinued because of adverse events (AEs). 37.9% of pts reported grade ≥3 AEs, the most common being anemia (16.4%). Since primary DCO, one new primary malignancy and four myelodysplastic syndrome events occurred. Conclusions: In final OS analyses, maintenance olaparib capsules showed consistent clinical activity in BRCAm and sBRCAm PSROC pts. Exploratory analyses suggest similar activity in non-BRCA HRRm pts. No new safety signals were observed. Findings highlight that PSROC pts, beyond those with a gBRCAm, can benefit from maintenance olaparib. Clinical trial information: NCT02476968. [Table: see text]