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Cited by 1,729PARP inhibition in cancer therapyBRCA gene mutations in cancerAdvanced Breast Cancer Therapies

Adjuvant Olaparib for Patients with BRCA1 - or BRCA2 -Mutated Breast Cancer

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Tutt, Andrew N.J., Garber, Judy E., Kaufman, Bella, Viale, Giuseppe, Fumagalli, Debora, Rastogi, Priya, Gelber, Richard D., de Azambuja, Evandro +31 more·2021·New England Journal of Medicine
DOI 10.1056/nejmoa2105215PMC PMC9126186
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Abstract

BACKGROUND: germline mutation-associated early breast cancer. METHODS: germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. RESULTS: A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P = 0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS: pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life. (Funded by the National Cancer Institute and AstraZeneca; OlympiA ClinicalTrials.gov number, NCT02032823.).

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  • Olaparib has shown substantial efficacy in various cancers, including ovarian, breast, and PCa.

    “Olaparib, has shown substantial efficacy in various cancers, including ovarian, breast, and PCa [26–28].”

    From Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer (2024) · cites this paper as [27]

    The Results > Efficacy section reports significantly longer invasive and distant disease–free survival with olaparib in patients with high-risk, BRCA-mutated early breast cancer. The introductory passage mentions proof-of-concept clinical activity in ovarian and prostate cancers, but this paper does not establish the claimed substantial efficacy of olaparib in those cancers. (LLM, conf=0.85)

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  1. [33]Pohl-Rescigno E, Hauke J, Loibl S, Association of germline variant status with therapy response in high-risk earlystage breast cancer: a secondary analysis of the GeparOcto randomized clinical trial. JAMA Oncol 2020; 6: 744– 8. 32163106 PMC7068666

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Authors
Tutt, A. N. J., Garber, J. E., Kaufman, B., Viale, G., Fumagalli, D., Rastogi, P., Gelber, R. D., de Azambuja, E., Fielding, A., Balmaña, J., Domchek, S. M., Gelmon, K. A., Hollingsworth, S. J., Korde, L. A., Linderholm, B., Bandos, H., Senkus, E., Suga, J. M., Shao, Z., Pippas, A. W., Nowecki, Z., Huzarski, T., Ganz, P. A., Lucas, P. C., Baker, N., Loibl, S., McConnell, R., Piccart, M., Schmutzler, R., Steger, G. G., Costantino, J. P., Arahmani, A., Wolmark, N., McFadden, E., Karantza, V., Lakhani, S. R., Yothers, G., Campbell, C., & Geyer, C. E.
Affiliations
  • Guy's Hospital (GB)
  • From the Breast Cancer Now Toby Robins Research Centre, the Institute of Cancer Research (A.N.J.T.), and the Breast Cancer Now Unit, Guy’s Hospital Cancer Centre, King’s College London (A.N.J.T.), London, AstraZeneca, Cambridge (S.J.H., N.B.), and Frontier Science (Scotland), Kincraig (R.M.C., E.M.F., C.C.) — all in the United Kingdom; Dana–Farber Cancer Institute, Harvard Medical School (J.E.G., R.D.G.), Frontier Science Foundation (R.D.G.), and Harvard T.H. Chan School of Public Health (R.D.G.) — all in Boston; the Breast Oncology Institute, Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (B.K.); the University of Milan, European Institute of Oncology IRCCS, Milan (G.V.); Breast International Group (D.F., A.A.) and Institut Jules Bordet, l’Université Libre de Bruxelles (E.A., M.P.), Brussels; NRG Oncology (P.R., H.B., P.C.L., N.W., G.Y., C.E.G.) and the Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania (S.M.D.), Philadelphia, and the UPMC Hillman Cancer Center (...
  • BC Cancer Agency (CA)
  • AstraZeneca (United Kingdom) (GB)
  • Northside Hospital (US)
  • Goethe University Frankfurt (DE)
  • Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
  • Houston Methodist (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2021-06-24
Volume
384
Issue
25
Pages
2394-2405
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2105215
PMC
PMC9126186
OpenAlex
W3165576985
Cited by
1,729
References
35
Citations by year
2026: 262 · 2025: 340 · 2024: 354 · 2023: 367 · 2022: 317 · 2021: 89
FWCI
103.37
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • BORIS (University Library Bern) (submittedVersion)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
  • Open Access CRIS of the University of Bern
Funders
  • AstraZeneca
  • Merck Sharp and Dohme
  • US National Cancer Institute (U10CA180822, U10CA180868, UG1CA189867)
Topics
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
Keywords
olaparib, BRCA1 mutation, BRCA2 mutation, hereditary breast cancer, adjuvant therapy, PARP inhibitors, invasive disease-free survival, distant disease-free survival, germline pathogenic variants, quality of life, early breast cancer, neoadjuvant chemotherapy, adjuvant chemotherapy, local therapy, PARP inhibitor resistance
MeSH terms
Poly(ADP-ribose) Polymerase Inhibitors, Adult, Antineoplastic Agents, Breast Neoplasms, Double-Blind Method, Female, Humans, Mastectomy, Middle Aged, Phthalazines, Piperazines, Chemotherapy, Adjuvant, Germ-Line Mutation, Disease-Free Survival, Erb-b2 Receptor Tyrosine Kinases, Receptor, ErbB-2, Genes, BRCA1, Genes, BRCA2

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