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
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved..
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 |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 33(2022), 12 vom: 15. Dez., Seite 1250-1268 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Geyer, C E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.12.2022 Date Revised 31.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.annonc.2022.09.159 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a 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 |
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| 500 | |a Date Revised 31.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BRCA1/2 | |
| 650 | 4 | |a PARP inhibition | |
| 650 | 4 | |a adjuvant therapy | |
| 650 | 4 | |a breast cancer | |
| 650 | 4 | |a olaparib | |
| 650 | 7 | |a olaparib |2 NLM | |
| 650 | 7 | |a WOH1JD9AR8 |2 NLM | |
| 650 | 7 | |a olympia |2 NLM | |
| 650 | 7 | |a 71714-89-1 |2 NLM | |
| 650 | 7 | |a Phthalazines |2 NLM | |
| 650 | 7 | |a BRCA1 protein, human |2 NLM | |
| 650 | 7 | |a BRCA1 Protein |2 NLM | |
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| 700 | 1 | |a Taboada, M |e verfasserin |4 aut | |
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| 700 | 1 | |a Rastogi, P |e verfasserin |4 aut | |
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| 700 | 1 | |a Arahmani, A |e verfasserin |4 aut | |
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| 700 | 1 | |a Arnedos, M |e verfasserin |4 aut | |
| 700 | 1 | |a Balmaña, J |e verfasserin |4 aut | |
| 700 | 1 | |a Bergh, J |e verfasserin |4 aut | |
| 700 | 1 | |a Bliss, J |e verfasserin |4 aut | |
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| 700 | 1 | |a Elsafy, F |e verfasserin |4 aut | |
| 700 | 1 | |a Fein, L E |e verfasserin |4 aut | |
| 700 | 1 | |a Fielding, A |e verfasserin |4 aut | |
| 700 | 1 | |a Ford, J M |e verfasserin |4 aut | |
| 700 | 1 | |a Friedman, S |e verfasserin |4 aut | |
| 700 | 1 | |a Gelmon, K A |e verfasserin |4 aut | |
| 700 | 1 | |a Gianni, L |e verfasserin |4 aut | |
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| 700 | 1 | |a Hollingsworth, S J |e verfasserin |4 aut | |
| 700 | 1 | |a Im, S-A |e verfasserin |4 aut | |
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| 700 | 1 | |a Španić, T |e verfasserin |4 aut | |
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| 700 | 1 | |a Yerushalmi, R |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, H |e verfasserin |4 aut | |
| 700 | 1 | |a Pang, D |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, K H |e verfasserin |4 aut | |
| 700 | 1 | |a Mailliez, A |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Z |e verfasserin |4 aut | |
| 700 | 1 | |a Tennevet, I |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, J |e verfasserin |4 aut | |
| 700 | 1 | |a Nagy, T |e verfasserin |4 aut | |
| 700 | 1 | |a Sonke, G S |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Q |e verfasserin |4 aut | |
| 700 | 1 | |a Parton, M |e verfasserin |4 aut | |
| 700 | 1 | |a Colleoni, M A |e verfasserin |4 aut | |
| 700 | 1 | |a Schmidt, M |e verfasserin |4 aut | |
| 700 | 1 | |a Brufsky, A M |e verfasserin |4 aut | |
| 700 | 1 | |a Razaq, W |e verfasserin |4 aut | |
| 700 | 1 | |a Kaufman, B |e verfasserin |4 aut | |
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| 700 | 1 | |a Öhler, Leopold |e investigator |4 oth | |
| 700 | 1 | |a Tinchon, Christoph |e investigator |4 oth | |
| 700 | 1 | |a Greil, Richard |e investigator |4 oth | |
| 700 | 1 | |a Heibl, Sonja |e investigator |4 oth | |
| 700 | 1 | |a Bartsch, Rupert |e investigator |4 oth | |
| 700 | 1 | |a Wette, Viktor |e investigator |4 oth | |
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| 700 | 1 | |a Stöger, Herbert |e investigator |4 oth | |
| 700 | 1 | |a Weltermann, Angsar |e investigator |4 oth | |
| 700 | 1 | |a Egle, Daniel |e investigator |4 oth | |
| 700 | 1 | |a Thiel, Irene |e investigator |4 oth | |
| 700 | 1 | |a Fuchs, David |e investigator |4 oth | |
| 700 | 1 | |a Rumpold, Holger |e investigator |4 oth | |
| 700 | 1 | |a Strasser-Weippl, Kathrin |e investigator |4 oth | |
| 700 | 1 | |a Rautenberg, Beate |e investigator |4 oth | |
| 700 | 1 | |a Müller, Volkmar |e investigator |4 oth | |
| 700 | 1 | |a Schmidt, Marcus |e investigator |4 oth | |
| 700 | 1 | |a Paepke, Stefan |e investigator |4 oth | |
| 700 | 1 | |a Aydogdu, Mustafa |e investigator |4 oth | |
| 700 | 1 | |a Thomssen, Christoph |e investigator |4 oth | |
| 700 | 1 | |a Rom, Joachim |e investigator |4 oth | |
| 700 | 1 | |a Mau, Christine |e investigator |4 oth | |
| 700 | 1 | |a Fasching, Peter |e investigator |4 oth | |
| 700 | 1 | |a Göhring, Uwe-Jochen |e investigator |4 oth | |
| 700 | 1 | |a Kühn, Thorsten |e investigator |4 oth | |
| 700 | 1 | |a Noeding, Stefanie |e investigator |4 oth | |
| 700 | 1 | |a Kümmel, Sherko |e investigator |4 oth | |
| 700 | 1 | |a Hackmann, John |e investigator |4 oth | |
| 700 | 1 | |a Stickeler, Elmar |e investigator |4 oth | |
| 700 | 1 | |a Joshi, Abhishek |e investigator |4 oth | |
| 700 | 1 | |a Dewar, Joanna |e investigator |4 oth | |
| 700 | 1 | |a Friedlander, Michael |e investigator |4 oth | |
| 700 | 1 | |a Phillips, Kelly-Anne |e investigator |4 oth | |
| 700 | 1 | |a Antill, Yoland |e investigator |4 oth | |
| 700 | 1 | |a Woodward, Natasha |e investigator |4 oth | |
| 700 | 1 | |a Abdi, Ehtesham |e investigator |4 oth | |
| 700 | 1 | |a Tiley, Susan |e investigator |4 oth | |
| 700 | 1 | |a George, Mathew |e investigator |4 oth | |
| 700 | 1 | |a Boadle, David |e investigator |4 oth | |
| 700 | 1 | |a Goodwin, Annabel |e investigator |4 oth | |
| 700 | 1 | |a van der Westhuizen, Andre |e investigator |4 oth | |
| 700 | 1 | |a Kannourakis, George |e investigator |4 oth | |
| 700 | 1 | |a Murray, Nicholas |e investigator |4 oth | |
| 700 | 1 | |a McCarthy, Nicole |e investigator |4 oth | |
| 700 | 1 | |a Kroep, Judith |e investigator |4 oth | |
| 700 | 1 | |a de Boer, Maaike |e investigator |4 oth | |
| 700 | 1 | |a Heijns, Joan |e investigator |4 oth | |
| 700 | 1 | |a Jager, Agnes |e investigator |4 oth | |
| 700 | 1 | |a Erdkamp, Franciscus |e investigator |4 oth | |
| 700 | 1 | |a Bakker, Sandra |e investigator |4 oth | |
| 700 | 1 | |a Sonke, Gabe S |e investigator |4 oth | |
| 700 | 1 | |a Sami, Amer |e investigator |4 oth | |
| 700 | 1 | |a Mackey, John |e investigator |4 oth | |
| 700 | 1 | |a Prady, Catherine |e investigator |4 oth | |
| 700 | 1 | |a Eisen, Andrea |e investigator |4 oth | |
| 700 | 1 | |a Desbiens, Christine |e investigator |4 oth | |
| 700 | 1 | |a Patocskai, Erica |e investigator |4 oth | |
| 700 | 1 | |a Ferrario, Cristiano |e investigator |4 oth | |
| 700 | 1 | |a Gelmon, Karen |e investigator |4 oth | |
| 700 | 1 | |a Bordeleau, Louise |e investigator |4 oth | |
| 700 | 1 | |a Chalchal, Haji |e investigator |4 oth | |
| 700 | 1 | |a Niraula, Saroj |e investigator |4 oth | |
| 700 | 1 | |a Ido Wolf |e investigator |4 oth | |
| 700 | 1 | |a Senkus, Elżbieta |e investigator |4 oth | |
| 700 | 1 | |a Duhoux, François |e investigator |4 oth | |
| 700 | 1 | |a Randal d'Hondt |e investigator |4 oth | |
| 700 | 1 | |a Luce, Sylvie |e investigator |4 oth | |
| 700 | 1 | |a Roodenbeke, Daphné t'Kint de |e investigator |4 oth | |
| 700 | 1 | |a Papadimitriou, Konstantinos |e investigator |4 oth | |
| 700 | 1 | |a Borms, Marleen |e investigator |4 oth | |
| 700 | 1 | |a Quaghebeur, Claire |e investigator |4 oth | |
| 700 | 1 | |a Jacot, William |e investigator |4 oth | |
| 700 | 1 | |a Brain, Etienne |e investigator |4 oth | |
| 700 | 1 | |a Venat-Bouvet, Laurence |e investigator |4 oth | |
| 700 | 1 | |a Lortholary, Alain |e investigator |4 oth | |
| 700 | 1 | |a Nowecki, Zbigniew |e investigator |4 oth | |
| 700 | 1 | |a Cardoso, Fátima |e investigator |4 oth | |
| 700 | 1 | |a Hayward, Richard |e investigator |4 oth | |
| 700 | 1 | |a Bella, Santiago |e investigator |4 oth | |
| 700 | 1 | |a Lazzaro, Mauricio Fernández |e investigator |4 oth | |
| 700 | 1 | |a Pilnik, Norma |e investigator |4 oth | |
| 700 | 1 | |a Fein, Luis E |e investigator |4 oth | |
| 700 | 1 | |a Blajman, Cesar |e investigator |4 oth | |
| 700 | 1 | |a Lerzo, Guillermo |e investigator |4 oth | |
| 700 | 1 | |a Varela, Mirta |e investigator |4 oth | |
| 700 | 1 | |a Zarba, Juan Jose |e investigator |4 oth | |
| 700 | 1 | |a Kaen, Diego |e investigator |4 oth | |
| 700 | 1 | |a Constanzo, Maria Victoria |e investigator |4 oth | |
| 700 | 1 | |a Tio, Joke |e investigator |4 oth | |
| 700 | 1 | |a Siggelkow, Wulf |e investigator |4 oth | |
| 700 | 1 | |a Jackisch, Christian |e investigator |4 oth | |
| 700 | 1 | |a Grischke, Eva Maria |e investigator |4 oth | |
| 700 | 1 | |a Zahm, Dirk |e investigator |4 oth | |
| 700 | 1 | |a Tato-Varela, Sara |e investigator |4 oth | |
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