Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation
Open accessAbstract
BACKGROUND: Olaparib is an oral poly(adenosine diphosphate-ribose) polymerase inhibitor that has promising antitumor activity in patients with metastatic breast cancer and a germline BRCA mutation. METHODS: We conducted a randomized, open-label, phase 3 trial in which olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease. Patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or standard therapy with single-agent chemotherapy of the physician's choice (capecitabine, eribulin, or vinorelbine in 21-day cycles). The primary end point was progression-free survival, which was assessed by blinded independent central review and was analyzed on an intention-to-treat basis. RESULTS: Of the 302 patients who underwent randomization, 205 were assigned to receive olaparib and 97 were assigned to receive standard therapy. Median progression-free survival was significantly longer in the olaparib group than in the standard-therapy group (7.0 months vs. 4.2 months; hazard ratio for disease progression or death, 0.58; 95% confidence interval, 0.43 to 0.80; P<0.001). The response rate was 59.9% in the olaparib group and 28.8% in the standard-therapy group. The rate of grade 3 or higher adverse events was 36.6% in the olaparib group and 50.5% in the standard-therapy group, and the rate of treatment discontinuation due to toxic effects was 4.9% and 7.7%, respectively. CONCLUSIONS: Among patients with HER2-negative metastatic breast cancer and a germline BRCA mutation, olaparib monotherapy provided a significant benefit over standard therapy; median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with olaparib monotherapy than with standard therapy. (Funded by AstraZeneca; OlympiAD ClinicalTrials.gov number, NCT02000622 .).
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Olaparib has been approved for treating metastatic breast cancer and mCRPC patients harboring genetic mutations in HRR genes.
“Olaparib, a PARP inhibitor, has garnered approval for treating metastatic breast cancer and mCRPC patients harboring genetic mutations in HRR genes [28, 39].”
From Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer (2024) · cites this paper as [39]
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- Authors
- Robson, M., Im, S.-A., Senkus, E., Xu, B., Domchek, S. M., Masuda, N., Delaloge, S., Li, W., Tung, N., Armstrong, A., Wu, W., Goessl, C., Runswick, S., & Conte, P.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Beth Israel Deaconess Medical Center (US)
- AstraZeneca (United Kingdom) (GB)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-08-10
- Volume
- 377
- Issue
- 6
- Pages
- 523-533
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2621271973
- Cited by
- 3,294
- References
- 2
- Citations by year
- 2026: 286 · 2025: 335 · 2024: 361 · 2023: 433 · 2022: 421 · 2021: 461 · 2020: 395 · 2019: 319 · 2018: 224 · 2017: 54 · 2016: 3 · 2013: 1
- FWCI
- 119.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Keywords
- olaparib, PARP inhibitors, germline BRCA mutation, metastatic breast cancer, HER2-negative breast cancer, progression-free survival, capecitabine, eribulin, vinorelbine, single-agent chemotherapy, PARP inhibitor monotherapy
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Adult, Aged, Antineoplastic Agents, Breast Neoplasms, Female, Humans, Middle Aged, Neoplasm Metastasis, Phthalazines, Piperazines, Chemotherapy, Adjuvant, Germ-Line Mutation, Disease-Free Survival, Erb-b2 Receptor Tyrosine Kinases, Receptor, ErbB-2, Genes, BRCA1, Genes, BRCA2, Kaplan-Meier Estimate, Young Adult
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