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

Geyer, CE, Jr; Garber, JE; Gelber, RD; Yothers, G; Taboada, M; Ross, L; Rastogi, P; Cui, K; Arahmani, A; Aktan, G; Armstrong, AC; Arnedos, M; Balmana, J; Bergh, J; Bliss, J; Delaloge, S; Domchek, SM; Eisen, A; Elsafy, F; Fein, LE; Fielding, A; Ford, JM; Friedman, S; Gelmon, KA; Gianni, L; Gnant, M; Hollingsworth, SJ; Im, SA; Jager, A; Johannsson, OT; Lakhani, SR; Janni, W; Linderholm, B; Liu, TW; Loman, N; Korde, L; Loibl, S; Lucas, PC; Marme, F; Martinez de Duenas, E; McConnell, R; Phillips, KA; Piccart, M; Rossi, G; Schmutzler, R; Senkus, E; Shao, Z; Sharma, P; Singer, CF; Spanic, T; Stickeler, E; Toi, M; Traina, TA; Viale, G; Zoppoli, G; Park, YH; Yerushalmi, R; Yang, H; Pang, D; Jung, KH; Mailliez, A; Fan, Z; Tennevet, I; Zhang, J; Nagy, T; Sonke, GS; Sun, Q; Parton, M; Colleoni, MA; Schmidt, M; Brufsky, AM; Razaq, W; Kaufman, B; Cameron, D; Campbell, C; Tutt, ANJ; OlympiA Clinical Trial Steering Committee and Investigators

Author(s): Geyer, CE, Jr; Garber, JE; Gelber, RD; Yothers, G; Taboada, M; Ross, L; Rastogi, P; Cui, K; Arahmani, A; Aktan, G; Armstrong, AC; Arnedos, M; Balmana, J; Bergh, J; Bliss, J; Delaloge, S; Domchek, SM; Eisen, A; Elsafy, F; Fein, LE; Fielding, A; Ford, JM; Friedman, S; Gelmon, KA; Gianni, L; Gnant, M; Hollingsworth, SJ; Im, SA; Jager, A; Johannsson, OT; Lakhani, SR; Janni, W; Linderholm, B; Liu, TW; Loman, N; Korde, L; Loibl, S; Lucas, PC; Marme, F; Martinez de Duenas, E; McConnell, R; Phillips, KA; Piccart, M; Rossi, G; Schmutzler, R; Senkus, E; Shao, Z; Sharma, P; Singer, CF; Spanic, T; Stickeler, E; Toi, M; Traina, TA; Viale, G; Zoppoli, G; Park, YH; Yerushalmi, R; Yang, H; Pang, D; Jung, KH; Mailliez, A; Fan, Z; Tennevet, I; Zhang, J; Nagy, T; Sonke, GS; Sun, Q; Parton, M; Colleoni, MA; Schmidt, M; Brufsky, AM; Razaq, W; Kaufman, B; Cameron, D; Campbell, C; Tutt, ANJ; OlympiA Clinical Trial Steering Committee and Investigators;
Details: Publication Year 2022-12,Volume 33,Issue #12,Page 1250-1268
Journal Title: Annals of Oncology
Publication Type: Research article
Abstract: 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 3.5 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 IDFS and DDFS with no new safety signals.
Keywords: Humans; Female; *Breast Neoplasms/drug therapy/genetics; Phthalazines/adverse effects; Germ Cells/pathology; BRCA1 Protein/genetics; Brca1/2; PARP inhibition; adjuvant therapy; breast cancer; olaparib
Department(s): Medical Oncology
PubMed ID: 36228963
Publisher's Version: https://doi.org/10.1016/j.annonc.2022.09.159
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-10-31 04:55:01

Last Modified: 2024-10-31 04:56:11