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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: original 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-r...

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Main Authors: Geyer, Charles Edward, Jr. (Author) , Garber, J. E. (Author) , Gelber, R. D. (Author) , Yothers, G. (Author) , Taboada, M. (Author) , Ross, L. (Author) , Rastogi, P. (Author) , Cui, K. (Author) , Arahmani, A. (Author) , Aktan, G. (Author) , Armstrong, A. C. (Author) , Arnedos, M. (Author) , Balmaña, J. (Author) , Bergh, J. (Author) , Bliss, J. (Author) , Delaloge, S. (Author) , Domchek, S. M. (Author) , Eisen, A. (Author) , Elsafy, F. (Author) , Fein, L. E. (Author) , Fielding, A. (Author) , Ford, J. M. (Author) , Friedman, S. (Author) , Gelmon, K. A. (Author) , Gianni, L. (Author) , Gnant, M. (Author) , Hollingsworth, S. J. (Author) , Im, S.-A. (Author) , Jager, A. (Author) , Jóhannsson, Ó. Þ (Author) , Lakhani, S. R. (Author) , Janni, W. (Author) , Linderholm, B. (Author) , Liu, T.-W. (Author) , Loman, N. (Author) , Korde, L. (Author) , Loibl, S. (Author) , Lucas, P. C. (Author) , Marmé, Frederik (Author) , Martinez de Dueñas, E. (Author) , McConnell, R. (Author) , Phillips, K.-A. (Author) , Piccart, M. (Author) , Rossi, G. (Author) , Schmutzler, R. (Author) , Senkus, E. (Author) , Shao, Z. (Author) , Sharma, P. (Author) , Singer, C. F. (Author) , Španić, T. (Author) , Stickeler, E. (Author) , Toi, M. (Author) , Traina, T. A. (Author) , Viale, G. (Author) , Zoppoli, G. (Author) , Park, Y. H. (Author) , Yerushalmi, R. (Author) , Yang, H. (Author) , Pang, D. (Author) , Jung, K. H. (Author) , Mailliez, A. (Author) , Fan, Z. (Author) , Tennevet, I. (Author) , Zhang, J. (Author) , Nagy, T. (Author) , Sonke, G. S. (Author) , Sun, Q. (Author) , Parton, M. (Author) , Colleoni, M. A. (Author) , Schmidt, M. (Author) , Brufsky, A. M. (Author) , Razaq, W. (Author) , Kaufman, B. (Author) , Cameron, D. (Author) , Campbell, C. (Author) , Tutt, A. N. J. (Author)
Format: Article (Journal)
Language:English
Published: 28 November 2022
In: Annals of oncology
Year: 2022, Volume: 33, Issue: 12, Pages: 1250-1268
ISSN:1569-8041
DOI:10.1016/j.annonc.2022.09.159
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.annonc.2022.09.159
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0923753422041655
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Author Notes:C.E. Geyer, Jr., J.E. Garber, R.D. Gelber, G. Yothers, M. Taboada, L. Ross, P. Rastogi, K. Cui, A. Arahmani, G. Aktan, A.C. Armstrong, M. Arnedos, J. Balmaña, J. Bergh, J. Bliss, S. Delaloge, S.M. Domchek, A. Eisen, F. Elsafy, L.E. Fein, A. Fielding, J.M. Ford, S. Friedman, K.A. Gelmon, L. Gianni, M. Gnant, S.J. Hollingsworth, S.-A. Im, A. Jager, Ó.Þ Jóhannsson, S.R. Lakhani, W. Janni, B. Linderholm, T.-W. Liu, N. Loman, L. Korde, S. Loibl, P.C. Lucas, F. Marmé, E. Martinez de Dueñas, R. McConnell, K.-A. Phillips, M. Piccart, G. Rossi, R. Schmutzler, E. Senkus, Z. Shao, P. Sharma, C.F. Singer, T. Španić, E. Stickeler, M. Toi, T.A. Traina, G. Viale, G. Zoppoli, Y.H. Park, R. Yerushalmi, H. Yang, D. Pang, K.H. Jung, A. Mailliez, Z. Fan, I. Tennevet, J. Zhang, T. Nagy, G.S. Sonke, Q. Sun, M. Parton, M.A. Colleoni, M. Schmidt, A.M. Brufsky, W. Razaq, B. Kaufman, D. Cameron, C. Campbell and A.N.J. Tutt, and the OlympiA Clinical Trial Steering Committee and Investigators
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Summary: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.
Item Description:Gesehen am 05.06.2023
Online veröffentlicht: 10 October 2022, Artikelversion: 28 November 2022
Physical Description:Online Resource
ISSN:1569-8041
DOI:10.1016/j.annonc.2022.09.159

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