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.
Date
2022-10-10Author
Geyer, CE
Garber, JE
Gelber, RD
Yothers, G
Taboada, M
Ross, L
Rastogi, P
Cui, K
Arahmani, A
Aktan, G
Armstrong, AC
Arnedos, M
Balmaña, 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, S-A
Jager, A
Jóhannsson, ÓÞ
Lakhani, SR
Janni, W
Linderholm, B
Liu, T-W
Loman, N
Korde, L
Loibl, S
Lucas, PC
Marmé, F
Martinez de Dueñas, E
McConnell, R
Phillips, K-A
Piccart, M
Rossi, G
Schmutzler, R
Senkus, E
Shao, Z
Sharma, P
Singer, CF
Španić, 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,
Type
Journal Article
Metadata
Show full item recordAbstract
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 (Δ 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% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 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.
Collections
Subject
BRCA1/2
Breast cancer
PARP inhibition
adjuvant therapy
olaparib
Research team
Directorate Breast Canc
Language
eng
Date accepted
2022-09-22
License start date
2022-10-10
Citation
Annals of Oncology, 2022, pp. S0923-7534(22)04165-5 -
Publisher
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