Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer.

摘要: 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 patients BRCA1 or BRCA2 germline mutation-associated early breast cancer. METHODS We conducted a phase 3, double-blind, randomized trial involving human epidermal growth factor receptor 2 (HER2)-negative cancer pathogenic likely variants and high-risk clinicopathological factors who had received local treatment neoadjuvant adjuvant chemotherapy. Patients were randomly assigned (in 1:1 ratio) 1 year of oral olaparib placebo. The primary end point was invasive disease-free survival. RESULTS A total 1836 underwent randomization. At prespecified event-driven interim analysis median follow-up 2.5 years, the 3-year survival 85.9% group 77.1% placebo (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 13.0; hazard ratio for disease death, 0.58; 99.5% CI, 0.41 0.82; P<0.001). distant 87.5% 80.4% 7.1 3.0 11.1; 0.57; 0.39 0.83; Olaparib associated fewer deaths than (59 86, respectively) (hazard ratio, 0.68; 99% 0.44 1.05; P = 0.02); however, between-group difference not significant at an interim-analysis boundary P value less 0.01. Safety data consistent known side effects olaparib, no excess serious adverse events special interest. CONCLUSIONS Among high-risk, HER2-negative variants, after completion chemotherapy significantly longer free limited on global patient-reported quality life. (Funded National Cancer Institute AstraZeneca; OlympiA ClinicalTrials.gov number, NCT02032823.).