dc.contributor.author |
OlympiA Clinical Trial Steering Committee and Investigators |
dc.date.accessioned |
2023-03-17T01:03:24Z |
dc.date.available |
2023-03-17T01:03:24Z |
dc.date.issued |
2022-12-01 |
dc.identifier.citation |
OlympiA Clinical Trial Steering Committee and Investigators 2022 , ' 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 ' , Annals of Oncology , vol. 33 , no. 12 , pp. 1250-1268 . https://doi.org/10.1016/j.annonc.2022.09.159 |
dc.identifier.issn |
0923-7534 |
dc.identifier.other |
94392298 |
dc.identifier.other |
44019be8-5ebc-4faa-a580-ebba08310350 |
dc.identifier.other |
85141805158 |
dc.identifier.other |
36228963 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/4075 |
dc.description |
Publisher Copyright: © 2022 The Authors |
dc.description.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 (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. |
dc.format.extent |
19 |
dc.format.extent |
978796 |
dc.format.extent |
1250-1268 |
dc.language.iso |
en |
dc.relation.ispartofseries |
Annals of Oncology; 33(12) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Krabbameinslæknisfræði |
dc.subject |
adjuvant therapy |
dc.subject |
BRCA1/2 |
dc.subject |
breast cancer |
dc.subject |
olaparib |
dc.subject |
PARP inhibition |
dc.subject |
Hematology |
dc.subject |
Oncology |
dc.title |
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 |
dc.type |
/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article |
dc.description.version |
Peer reviewed |
dc.identifier.doi |
10.1016/j.annonc.2022.09.159 |
dc.relation.url |
http://www.scopus.com/inward/record.url?scp=85141805158&partnerID=8YFLogxK |
dc.contributor.department |
Other departments |