dc.contributor.author | Geyer, CE | |
dc.contributor.author | Garber, JE | |
dc.contributor.author | Gelber, RD | |
dc.contributor.author | Yothers, G | |
dc.contributor.author | Taboada, M | |
dc.contributor.author | Ross, L | |
dc.contributor.author | Rastogi, P | |
dc.contributor.author | Cui, K | |
dc.contributor.author | Arahmani, A | |
dc.contributor.author | Aktan, G | |
dc.contributor.author | Armstrong, AC | |
dc.contributor.author | Arnedos, M | |
dc.contributor.author | Balmaña, J | |
dc.contributor.author | Bergh, J | |
dc.contributor.author | Bliss, J | |
dc.contributor.author | Delaloge, S | |
dc.contributor.author | Domchek, SM | |
dc.contributor.author | Eisen, A | |
dc.contributor.author | Elsafy, F | |
dc.contributor.author | Fein, LE | |
dc.contributor.author | Fielding, A | |
dc.contributor.author | Ford, JM | |
dc.contributor.author | Friedman, S | |
dc.contributor.author | Gelmon, KA | |
dc.contributor.author | Gianni, L | |
dc.contributor.author | Gnant, M | |
dc.contributor.author | Hollingsworth, SJ | |
dc.contributor.author | Im, S-A | |
dc.contributor.author | Jager, A | |
dc.contributor.author | Jóhannsson, ÓÞ | |
dc.contributor.author | Lakhani, SR | |
dc.contributor.author | Janni, W | |
dc.contributor.author | Linderholm, B | |
dc.contributor.author | Liu, T-W | |
dc.contributor.author | Loman, N | |
dc.contributor.author | Korde, L | |
dc.contributor.author | Loibl, S | |
dc.contributor.author | Lucas, PC | |
dc.contributor.author | Marmé, F | |
dc.contributor.author | Martinez de Dueñas, E | |
dc.contributor.author | McConnell, R | |
dc.contributor.author | Phillips, K-A | |
dc.contributor.author | Piccart, M | |
dc.contributor.author | Rossi, G | |
dc.contributor.author | Schmutzler, R | |
dc.contributor.author | Senkus, E | |
dc.contributor.author | Shao, Z | |
dc.contributor.author | Sharma, P | |
dc.contributor.author | Singer, CF | |
dc.contributor.author | Španić, T | |
dc.contributor.author | Stickeler, E | |
dc.contributor.author | Toi, M | |
dc.contributor.author | Traina, TA | |
dc.contributor.author | Viale, G | |
dc.contributor.author | Zoppoli, G | |
dc.contributor.author | Park, YH | |
dc.contributor.author | Yerushalmi, R | |
dc.contributor.author | Yang, H | |
dc.contributor.author | Pang, D | |
dc.contributor.author | Jung, KH | |
dc.contributor.author | Mailliez, A | |
dc.contributor.author | Fan, Z | |
dc.contributor.author | Tennevet, I | |
dc.contributor.author | Zhang, J | |
dc.contributor.author | Nagy, T | |
dc.contributor.author | Sonke, GS | |
dc.contributor.author | Sun, Q | |
dc.contributor.author | Parton, M | |
dc.contributor.author | Colleoni, MA | |
dc.contributor.author | Schmidt, M | |
dc.contributor.author | Brufsky, AM | |
dc.contributor.author | Razaq, W | |
dc.contributor.author | Kaufman, B | |
dc.contributor.author | Cameron, D | |
dc.contributor.author | Campbell, C | |
dc.contributor.author | Tutt, ANJ | |
dc.contributor.author | OlympiA Clinical Trial Steering Committee and Investigators, | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-10-17T08:32:33Z | |
dc.date.available | 2022-10-17T08:32:33Z | |
dc.date.issued | 2022-10-10 | |
dc.identifier | S0923-7534(22)04165-5 | |
dc.identifier.citation | Annals of Oncology, 2022, pp. S0923-7534(22)04165-5 - | |
dc.identifier.issn | 0923-7534 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5532 | |
dc.identifier.eissn | 1569-8041 | |
dc.identifier.eissn | 1569-8041 | |
dc.identifier.doi | 10.1016/j.annonc.2022.09.159 | |
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 | Print-Electronic | |
dc.format.extent | S0923-7534(22)04165-5 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | Annals of Oncology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | BRCA1/2 | |
dc.subject | Breast cancer | |
dc.subject | PARP inhibition | |
dc.subject | adjuvant therapy | |
dc.subject | olaparib | |
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 | Journal Article | |
dcterms.dateAccepted | 2022-09-22 | |
dc.date.updated | 2022-10-17T08:26:08Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.annonc.2022.09.159 | |
rioxxterms.licenseref.startdate | 2022-10-10 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36228963 | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.annonc.2022.09.159 | |
icr.researchteam | Directorate Breast Canc | |
dc.contributor.icrauthor | Bliss, Judith | |
dc.contributor.icrauthor | Tutt, Andrew | |
icr.provenance | Deposited by Ms Alexandra Carroll (impersonating Prof Andrew Tutt) on 2022-10-17. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S0923753422041655-main.pdf | |