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 / 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

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..

Medienart:

E-Artikel

Erscheinungsjahr:

28 November 2022

2022

Erschienen:

28 November 2022

Enthalten in:

Zur Gesamtaufnahme - volume:33

Enthalten in:

Annals of oncology - 33(2022), 12 vom: Dez., Seite 1250-1268

Sprache:

Englisch

Weiterer Titel:

phase three BRCAone/two BRCA one two

Beteiligte Personen:

Geyer, Charles Edward [VerfasserIn]
Garber, J. E. [VerfasserIn]
Gelber, R. D. [VerfasserIn]
Yothers, G. [VerfasserIn]
Taboada, M. [VerfasserIn]
Ross, L. [VerfasserIn]
Rastogi, P. [VerfasserIn]
Cui, K. [VerfasserIn]
Arahmani, A. [VerfasserIn]
Aktan, G. [VerfasserIn]
Armstrong, A. C. [VerfasserIn]
Arnedos, M. [VerfasserIn]
Balmaña, J. [VerfasserIn]
Bergh, J. [VerfasserIn]
Bliss, J. [VerfasserIn]
Delaloge, S. [VerfasserIn]
Domchek, S. M. [VerfasserIn]
Eisen, A. [VerfasserIn]
Elsafy, F. [VerfasserIn]
Fein, L. E. [VerfasserIn]
Fielding, A. [VerfasserIn]
Ford, J. M. [VerfasserIn]
Friedman, S. [VerfasserIn]
Gelmon, K. A. [VerfasserIn]
Gianni, L. [VerfasserIn]
Gnant, M. [VerfasserIn]
Hollingsworth, S. J. [VerfasserIn]
Im, S.-A. [VerfasserIn]
Jager, A. [VerfasserIn]
Jóhannsson, Ó. Þ [VerfasserIn]
Lakhani, S. R. [VerfasserIn]
Janni, W. [VerfasserIn]
Linderholm, B. [VerfasserIn]
Liu, T.-W. [VerfasserIn]
Loman, N. [VerfasserIn]
Korde, L. [VerfasserIn]
Loibl, S. [VerfasserIn]
Lucas, P. C. [VerfasserIn]
Marmé, Frederik, 1974- [VerfasserIn]
Martinez de Dueñas, E. [VerfasserIn]
McConnell, R. [VerfasserIn]
Phillips, K.-A. [VerfasserIn]
Piccart, M. [VerfasserIn]
Rossi, G. [VerfasserIn]
Schmutzler, R. [VerfasserIn]
Senkus, E. [VerfasserIn]
Shao, Z. [VerfasserIn]
Sharma, P. [VerfasserIn]
Singer, C. F. [VerfasserIn]
Španić, T. [VerfasserIn]
Stickeler, E. [VerfasserIn]
Toi, M. [VerfasserIn]
Traina, T. A. [VerfasserIn]
Viale, G. [VerfasserIn]
Zoppoli, G. [VerfasserIn]
Park, Y. H. [VerfasserIn]
Yerushalmi, R. [VerfasserIn]
Yang, H. [VerfasserIn]
Pang, D. [VerfasserIn]
Jung, K. H. [VerfasserIn]
Mailliez, A. [VerfasserIn]
Fan, Z. [VerfasserIn]
Tennevet, I. [VerfasserIn]
Zhang, J. [VerfasserIn]
Nagy, T. [VerfasserIn]
Sonke, G. S. [VerfasserIn]
Sun, Q. [VerfasserIn]
Parton, M. [VerfasserIn]
Colleoni, M. A. [VerfasserIn]
Schmidt, M. [VerfasserIn]
Brufsky, A. M. [VerfasserIn]
Razaq, W. [VerfasserIn]
Kaufman, B. [VerfasserIn]
Cameron, D. [VerfasserIn]
Campbell, C. [VerfasserIn]
Tutt, A. N. J. [VerfasserIn]

Links:

Volltext [lizenzpflichtig]
Volltext [lizenzpflichtig]

Themen:

Adjuvant therapy
Breast cancer
Olaparib
PARP inhibition

Anmerkungen:

Gesehen am 05.06.2023

Online veröffentlicht: 10 October 2022, Artikelversion: 28 November 2022

Umfang:

19

doi:

10.1016/j.annonc.2022.09.159

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

1847425054

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