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Geyer, C. E.; 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, Barbro; Liu, T. W.; Loman, N.; Korde, L.; Loibl, S.; Lucas, P. C.; Marme, F.; de Duenas, E. M.; McConnell, R.; Phillips, K. A.; Piccart, M.; Rossi, G.; Schmutzler, R.; Senkus, E.; Shao, Z.; Sharma, P.; Singer, C. F.; Spanic, T.; Stickeler, E.; Toi, M.; Traina, T. A.; Viale, G.; Zoppoli, G.; Park, Y. H.; Yerushalmi, R.; Yang, H.; Pang, D.; Jung, K. H.; Mailliez, A.; Fan, Z.; Tennevet, I.; Zhang, J.; Nagy, T.; Sonke, G. S.; Sun, Q.; Parton, M.; Colleoni, M. A.; Schmidt, M.; Brufsky, A. M.; Razaq, W.; Kaufman, B.; Cameron, D.; Campbell, C.; Tutt, A. N. J.; Johannsson, O. T.
Annals of oncology, 12/2022, Letnik: 33, Številka: 12Journal Article
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.
