Olaparib in HR-deficient, metastatic triple-negative breast and platinum-sensitive relapsed ovarian cancers without germline mutations in BRCA1/2: phase 2 EMBRACE trial

Sep 22, 2026

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Phase 2 EMBRACE evaluated olaparib in platinum-sensitive relapsed high-grade serous ovarian cancer (PSROC) and metastatic triple-negative breast cancer (mTNBC) with non-germline BRCA1/2 homologous recombination deficiency (HRD). Olaparib 300 mg twice daily was given in a single-arm design; promoter methylation and HR gene status were assessed using methylation-sensitive high-resolution melting PCR and targeted sequencing, with mutation testing for unmethylated cases. Primary endpoint was objective tumour response rate (OTRR) at 6 months, with progression-free survival and safety as secondary outcomes. Results showed OTRR of 40% in HGSOC and 0% in TNBC.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

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Background

Methods

Results

Conclusions

Clinical trials registration

[www.nature.com/bjc](www.nature.com/bjc British)[ British](www.nature.com/bjc British) Journal of Cancer ARTICLE OPEN Translational Therapeutics Olaparib in HR-deﬁcient, metastatic triple-negative breast and platinum-sensitive relapsed ovarian cancers without germline mutations in BRCA1/2: phase 2 EMBRACE trial Katrin M. Sjoquist 1,2,3 ✉ , Alexander Dobrovic4,21, Kristy P. Robledo1, Ksenija Nesic5,6, Sally Baron-Hay 7,8, Sumitra Ananda3,9, Nicole McCarthy8,10, Jeffrey Goh3,11, Christopher Steer 12,13, Nick Murray8,14, Sonia Yip1, Linda R. Mileshkin 3,9,15, J. Lynn Fink16, Garry Chang1, Lisa Bailey1, Yvonne Lee 1, Danka S. Zebic 1,17, U. G. Imalki U. Kariyawasam 5,6, Kristy Shield-Artin 5,6, Andrew Jarratt5,6, Justin Bedő5,6, Anthony T. Papenfuss5,6, Olga Kondrashova 5,18, Matthew J. Wakeﬁeld5,19, Cassandra J. Vandenberg 5,6, Martin R. Stockler 1, Clare L. Scott3,5,9,19,22 and Paul M. Waring 16,20,22 © The Author(s) 2026 | | BACKGROUND: Homologous recombination (HR) deﬁciency (HRD) from germline BRCA1/2 mutations (gBRCAm) sensitizes highgrade 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 nonBRCA 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 patientselection for PARPi | | | --- | --- | --- | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | .
CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry Registration number ACTRN 12617000855325 . | | | | | British Journal of Cancer (2026) 135:1152–1163; [https://doi.org/10.1038/s41416-026-03535-6](https://doi.org/10.1038/s41416-026-03535-6) | | | | | | BACKGROUND Despite current best treatments, advanced breast and ovarian cancers remain a signiﬁcant clinical challenge. Better treatment options are needed to improve survival of women with relapsed high-grade serous ovarian cancer (HGSOC) and metastatic triple negative (ER-, PR-, HER2-) breast cancer (TNBC) . Poly(ADP-ribose) polymerase inhibitors (PARPi), such as olaparib, have been in clinical use for nearly a decade, with improved outcomes in selected patients with breast [1, 2] and ovarian cancers in patients with germline BRCA1/2 pathogenic variants (PV) (gBRCAm) [3] and prostate cancers harbouring germline or somatic PV in genes involved in homologous recombination (HR) DNA repair (HR genes) [4] . With increasing evidence for efﬁcacy of PARPi in HR deﬁcient (HRD) breast, ovarian and prostate cancers without 1NHMRC Clinical Trials Centre, The University of Sydney, Camperdown, Australia. 2Cancer Care Centre, St George Hospital, Kogarah, Australia. 3Australia New Zealand Gynaecological Oncology Group, Sydney, Australia. 4Department of Surgery, The University of Melbourne, Parkville, Australia. 5Walter and Eliza Hall Institute of Me

FAQs

What was the primary endpoint of the EMBRACE phase 2 trial?

The primary endpoint was objective tumour response rate (OTRR) at 6 months.

How were HRD subtypes determined in this study?

Tumour meBRCA1/meRAD51C was assessed using methylation-sensitive, high-resolution melting PCR, and unmethylated cases underwent HR gene mutation testing via targeted sequencing.

What were the key response outcomes for HGSOC and TNBC?

At 6 months, OTRR was 40% for HGSOC and 0% for TNBC, with 6- and 12-month progression-free survival of 53%/25% in HGSOC and 17%/0% in TNBC.

Sep 22, 2026

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