Olaparib in HR-deficient, metastatic triple-negative breast and platinum-sensitive relapsed ovarian cancers without germline mutations in BRCA1/2: phase 2 EMBRACE trial
- Author(s)
- Sjoquist, KM; Dobrovic, A; Robledo, KP; Nesic, K; Baron-Hay, S; Ananda, S; Mccarthy, N; Goh, J; Steer, C; Murray, N; Yip, S; Mileshkin, LR; Fink, JL; Chang, G; Bailey, L; Lee, Y; Zebic, DS; Kariyawasam, Ugiu; Shield-Artin, K; Jarratt, A; Bedő, J; Papenfuss, AT; Kondrashova, O; Wakefield, MJ; Vandenberg, CJ; Stockler, MR; Scott, CL; Waring, PM;
- Journal Title
- British Journal of Cancer
- Publication Type
- Jul 8
- Abstract
- BACKGROUND: Homologous recombination (HR) deficiency (HRD) from germline BRCA1/2 mutations (gBRCAm) sensitizes high-grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC) to PARP inhibitors (PARPi), as may promoter methylation of BRCA1 (meBRCA1) or RAD51C (meRAD51C) or mutation of non-BRCA HR genes. This trial evaluated olaparib in platinum-sensitive, relapsed HGSOC (PSROC) and metastatic TNBC (mTNBC) with non-gBRCA HRD. METHODS: Single-arm phase 2 trial of olaparib 300 mg orally twice daily. Tumour meBRCA1/meRAD51C determined by methylation-sensitive, high-resolution melting PCR and targeted sequencing. Unmethylated cases underwent HR gene mutation testing. PRIMARY OUTCOME: objective tumour response rate (OTRR) at 6 months(m). SECONDARY OUTCOMES: progression-free survival (PFS), OTRR according to HR gene aberration, and safety. RESULTS: Total 22 enrolled: promoter methylation detected in 8/15 HGSOC and 5/7 TNBC, and pathogenic variants (PV) in non-BRCA HR genes. OTRR at 6 m was 40% HGSOC and 0% TNBC. OTRR was 38% in methylated cases vs 43% for other HRD. 6 m/12 m PFS were 53% / 25% (HGSOC), and 17% / 0% (TNBC). CONCLUSIONS: Olaparib demonstrated activity in HGSOC beyond gBRCAm, including with meBRCA1 or gRAD51C PV. Olaparib had limited activity in pre-treated TNBC. Effects of prior chemotherapy on meBRCA1/meRAD51C require exploration to improve patient selection for PARPi. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry Registration number ACTRN 12617000855325.
- Publisher
- Springer Nature
- Research Division(s)
- Cancer Biology and Stem Cells; Bioinformatics and Computational Biology
- PubMed ID
- 42420629
- Publisher's Version
- https://doi.org/10.1038/s41416-026-03535-6
- Open Access at Publisher's Site
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Creation Date: 2026-07-15 09:14:54
Last Modified: 2026-07-15 09:15:02