Adjuvant olaparib for patients with BRCA1- Or BRCA2-mutated breast cancer

Andrew N.J. Tutt, Judy E. Garber, Bella Kaufman, Giuseppe Viale, Debora Fumagalli, Priya Rastogi, Richard D. Gelber, Evandro de Azambuja, Anitra Fielding, Judith Balmaña, Susan M. Domchek, Karen A. Gelmon, Simon J. Hollingsworth, Larissa A. Korde, Barbro Linderholm, Hanna Bandos, Elżbieta Senkus, Jennifer M. Suga, Zhimin Shao, Andrew W. PippasZbigniew Nowecki, Tomasz Huzarski, Patricia A. Ganz, Peter C. Lucas, Nigel Baker, Sibylle Loibl, Robin McConnell, Martine Piccart, Rita Schmutzler, Guenther G. Steger, Joseph P. Costantino, Amal Arahmani, Norman Wolmark, Eleanor McFadden, Vassiliki Karantza, Sunil R. Lakhani, Greg Yothers, Christine Campbell, Charles E. Geyer

Research output: Contribution to journalArticlepeer-review

601 Scopus citations


BACKGROUND Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation–associated early breast cancer. METHODS We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease–free survival. RESULTS A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease–free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease–free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life.

Original languageEnglish (US)
Pages (from-to)2394-2405
Number of pages12
JournalNew England Journal of Medicine
Issue number25
StatePublished - Jun 24 2021

ASJC Scopus subject areas

  • Medicine(all)


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