Geyer, C. E., Jr., 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, B., Liu, T-W, Loman, N., Korde, L., Loibl, S., Lucas, P. C., Marme, F., de Duenas, E. Martinez, 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. and Johannsson, O. Th (2022). Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann. Oncol., 33 (12). S. 1250 - 1269. AMSTERDAM: ELSEVIER. ISSN 1569-8041

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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 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Geyer, C. E., Jr.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garber, J. E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gelber, R. D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yothers, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taboada, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ross, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rastogi, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cui, K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arahmani, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aktan, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Armstrong, A. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnedos, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balmana, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergh, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bliss, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delaloge, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domchek, S. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eisen, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elsafy, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fein, L. E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fielding, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ford, J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedman, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gelmon, K. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gianni, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gnant, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hollingsworth, S. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Im, S-AUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jager, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lakhani, S. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janni, W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linderholm, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, T-WUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loman, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korde, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loibl, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lucas, P. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marme, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Duenas, E. MartinezUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McConnell, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phillips, K-AUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piccart, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rossi, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Senkus, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shao, Z.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sharma, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singer, C. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spanic, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stickeler, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toi, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Traina, T. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Viale, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zoppoli, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park, Y. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yerushalmi, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pang, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jung, K. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mailliez, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fan, Z.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tennevet, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nagy, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sonke, G. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sun, Q.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parton, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Colleoni, M. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brufsky, A. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Razaq, W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaufman, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cameron, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campbell, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tutt, A. N. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johannsson, O. ThUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-699461
DOI: 10.1016/j.annonc.2022.09.159
Journal or Publication Title: Ann. Oncol.
Volume: 33
Number: 12
Page Range: S. 1250 - 1269
Date: 2022
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1569-8041
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DNA-REPAIR DEFECT; MUTATION CARRIERS; STAGING SYSTEM; MUTANT-CELLS; CAPECITABINE; CHEMOTHERAPYMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69946

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