Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer

作者：Geyer, C. E., Jr.; Garber, J. E.; Gelber, R. D.; Yothers, G.; Taboada, M.; Ross, L.; Rastogi, P.; Cui, K.; Arahmani, A.; Aktan, G.; Armstrong, A. C.; Arnedos, M.; Balmana, J.; Bergh, J.; Bliss, J.; Delaloge, S.; Domchek, S. M.; Eisen, A.; Elsafy, F.; Fein, L. E.; Fielding, A.; Ford, J. M.; Friedman, S.; Gelmon, K. A.; Gianni, L.; Gnant, M.; Hollingsworth, S. J.; Im, S-A; Jager, A.; Lakhani, S. R.; Janni, W.; Linderholm, B.; Liu, T-W; Loman, N.; Korde, L.; Loibl, S.; Lucas, P. C.; Marme, F.

来源：Annals of Oncology, 2022, 33(12): 1250-1268.

DOI：10.1016/j.annonc.2022.09.159

• breast cancer
• BRCA1/2
• PARP inhibition
• olaparib
• adjuvant therapy

Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. @@@ Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. @@@ Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. @@@ Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.

• 单位
  中国科学院; 中国医学科学院北京协和医院; 哈尔滨医科大学; 6; 复旦大学; 吉林大学; 中国科学院研究生院