Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 2394-2405 |
| Number of pages | 12 |
| Journal | New Engl. J. Med. |
| Volume | 384 |
| Issue number | 25 |
| DOIs | |
| Publication status | Published - 2021 |
Keywords
- antineoplastic agent
- epidermal growth factor receptor 2
- ERBB2 protein, human
- nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor
- olaparib
- phthalazine derivative
- piperazine derivative
- adjuvant chemotherapy
- adult
- breast tumor
- clinical trial
- controlled study
- disease free survival
- double blind procedure
- female
- genetics
- germline mutation
- human
- mastectomy
- middle aged
- mortality
- multicenter study
- phase 3 clinical trial
- randomized controlled trial
- tumor suppressor gene
- Adult
- Antineoplastic Agents
- Breast Neoplasms
- Chemotherapy, Adjuvant
- Disease-Free Survival
- Double-Blind Method
- Female
- Genes, BRCA1
- Genes, BRCA2
- Germ-Line Mutation
- Humans
- Mastectomy
- Middle Aged
- Phthalazines
- Piperazines
- Poly(ADP-ribose) Polymerase Inhibitors
- Receptor, ErbB-2
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Adjuvant olaparib for patients with BRCA1- Or BRCA2-mutated breast cancer : New England Journal of Medicine. / Tutt, A.N.J.; Garber, J.E.; Kaufman, B. et al.
In: New Engl. J. Med., Vol. 384, No. 25, 2021, p. 2394-2405.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Adjuvant olaparib for patients with BRCA1- Or BRCA2-mutated breast cancer
T2 - New England Journal of Medicine
AU - Tutt, A.N.J.
AU - Garber, J.E.
AU - Kaufman, B.
AU - Viale, G.
AU - Fumagalli, D.
AU - Rastogi, P.
AU - Gelber, R.D.
AU - de Azambuja, E.
AU - Fielding, A.
AU - Balmaña, J.
AU - Domchek, S.M.
AU - Gelmon, K.A.
AU - Hollingsworth, S.J.
AU - Korde, L.A.
AU - Linderholm, B.
AU - Bandos, H.
AU - Senkus, E.
AU - Suga, J.M.
AU - Shao, Z.
AU - Pippas, A.W.
AU - Nowecki, Z.
AU - Huzarski, T.
AU - Ganz, P.A.
AU - Lucas, P.C.
AU - Baker, N.
AU - Loibl, S.
AU - McConnell, R.
AU - Piccart, M.
AU - Schmutzler, R.
AU - Steger, G.G.
AU - Costantino, J.P.
AU - Arahmani, A.
AU - Wolmark, N.
AU - McFadden, E.
AU - Karantza, V.
AU - Lakhani, S.R.
AU - Yothers, G.
AU - Campbell, C.
AU - Geyer C.E., Jr.
N1 - Cited By :10 Export Date: 1 October 2021 CODEN: NEJMA Correspondence Address: Tutt, A.N.J.; Breast Cancer Now Toby Robins Research Centre, 237 Fulham Rd., United Kingdom; email: andrew.tutt@icr.ac.uk Chemicals/CAS: epidermal growth factor receptor 2, 137632-09-8; olaparib, 763113-22-0; Antineoplastic Agents; ERBB2 protein, human; olaparib; Phthalazines; Piperazines; Poly(ADP-ribose) Polymerase Inhibitors; Receptor, ErbB-2 Funding details: National Cancer Institute, NCI Funding details: AstraZeneca Funding text 1: Supported by grants (U10CA180868, UG1CA189867, and U10CA180822) from the National Cancer Institute and funding and provision of olaparib and placebo by AstraZeneca as part of an alliance between AstraZeneca and Merck. References: Dorling, L., Carvalho, S., Allen, J., Breast cancer risk genes — Association analysis in more than 113,000 women (2021) N Engl J Med, 384, pp. 428-439; Hu, C., Hart, S.N., Gnanaolivu, R., A population-based study of genes previously implicated in breast cancer (2021) N Engl J Med, 384, pp. 440-451; Kuchenbaecker, K.B., Hopper, J.L., Barnes, D.R., Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers (2017) JAMA, 317, pp. 2402-2416; Mavaddat, N., Barrowdale, D., Andrulis, I.L., Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the consortium of Investigators of modifiers of BRCA1/2 (CIMBA) (2012) Cancer Epidemiol Biomarkers Prev, 21, pp. 134-147; Atchley, D.P., Albarracin, C.T., Lopez, A., Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer (2008) J Clin Oncol, 26, pp. 4282-4288; Lakhani, S.R., van de Vijver, M.J., Jacquemier, J., The pathology of familial breast cancer: Predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2 (2002) J Clin Oncol, 20, pp. 2310-8.. , https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf, NCCN genetic/familial high-risk assessment: breast and ovarian version 1. 2020. 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Fong, P.C., Boss, D.S., Yap, T.A., Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers (2009) N Engl J Med, 361, pp. 123-134; Tutt, A., Robson, M., Garber, J.E., Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: A proof-of-concept trial (2010) Lancet, 376, pp. 235-244; Audeh, M.W., Carmichael, J., Penson, R.T., Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: A proof-of-concept trial (2010) Lancet, 376, pp. 245-251; Kaufman, B., Shapira-Frommer, R., Schmutzler, R.K., Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation (2015) J Clin Oncol, 33, pp. 244-250; Shah, P.D., Patil, S., Dickler, M.N., Offit, K., Hudis, C.A., Robson, M.E., Twenty-one-gene recurrence score assay in BRCA-associated versus sporadic breast cancers: Differences based on germline mutation status (2016) Cancer, 122, pp. 1178-1184; Tryggvadottir, L., Olafsdottir, E.J., Olafsdottir, G.H., Tumour diploidy and survival in breast cancer patients with BRCA2 mutations (2013) Breast Cancer Res Treat, 140, pp. 375-384; Mittendorf, E.A., Jeruss, J.S., Tucker, S.L., Validation of a novel staging system for disease-specific survival in patients with breast cancer treated with neoadjuvant chemotherapy (2011) J Clin Oncol, 29, pp. 1956-1962; Hudis, C.A., Barlow, W.E., Costantino, J.P., Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: The steep system (2007) J Clin Oncol, 25, pp. 2127-2132; Stone, A., The application of bespoke spending functions in group-sequential designs and the effect of delayed treatment switching in survival trials (2010) Pharm Stat, 9, pp. 151-161; Cuzick, J., Forest plots and the interpretation of subgroups (2005) Lancet, 365, p. 1308; Robson, M., Im, S.A., Senkus, E., Olaparib for metastatic breast cancer in patients with a germline BRCA mutation (2017) N Engl J Med, 377, pp. 523-533; Litton, J.K., Rugo, H.S., Ettl, J., Talazoparib in patients with advanced breast cancer and a germline BRCA mutation (2018) N Engl J Med, 379, pp. 753-763; Fasching, P.A., Link, T., Hauke, J., Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study) Ann Oncol, 2021 (32), pp. 49-57; Burstein, H.J., Curigliano, G., Loibl, S., Estimating the benefits of therapy for early-stage breast cancer: The St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019 (2019) Ann Oncol, 30, pp. 1541-1557; NCCN clinical practice guidelines in oncology — Breast cancer version 5.2020 , p. 2021. , https://www2.tri-kobe.org/nccn/guideline/breast/english/breast.pdf, National Comprehensive Cancer Network, July 15; Tutt, A., Tovey, H., Cheang, M.C.U., Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: The TNT trial (2018) Nat Med, 24, pp. 628-637; Zhang, J., Lin, Y., Sun, X.J., Biomarker assessment of the CBCSG006 trial: A randomized phase III trial of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer (2018) Ann Oncol, 29, pp. 1741-1747; Murai, J., Huang, S.Y., Das, B.B., Trapping of PARP1 and PARP2 by clinical PARP inhibitors (2012) Cancer Res, 72, pp. 5588-5599; Morice, P.M., Leary, A., Dolladille, C., Myelodysplastic syndrome and acute myeloid leukaemia in patients treated with PARP inhibitors: A safety meta-analysis of randomised controlled trials and a retrospective study of the WHO pharmacovigilance database (2021) Lancet Haematol, 8 (2), pp. e122-e134; Pohl-Rescigno, E., Hauke, J., Loibl, S., Association of germline variant status with therapy response in high-risk early-stage breast cancer: A secondary analysis of the GeparOcto randomized clinical trial (2020) JAMA Oncol, (6), pp. 744-748; Masuda, N., Lee, S.J., Ohtani, S., Adjuvant capecitabine for breast cancer after preoperative chemotherapy (2017) N Engl J Med, 376, pp. 2147-2159; Robson, M.E., Tung, N., Conte, P., OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer (2019) Ann Oncol, 30, pp. 558-566; Tutt, A., Ashworth, A., Can genetic testing guide treatment in breast cancer? (2008) Eur J Cancer, 44, pp. 2774-2780
PY - 2021
Y1 - 2021
N2 - BACKGROUND Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation–associated early breast cancer. METHODS We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer with BRCA1 or BRCA2 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
AB - BACKGROUND Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation–associated early breast cancer. METHODS We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer with BRCA1 or BRCA2 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
KW - antineoplastic agent
KW - epidermal growth factor receptor 2
KW - ERBB2 protein, human
KW - nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor
KW - olaparib
KW - phthalazine derivative
KW - piperazine derivative
KW - adjuvant chemotherapy
KW - adult
KW - breast tumor
KW - clinical trial
KW - controlled study
KW - disease free survival
KW - double blind procedure
KW - female
KW - genetics
KW - germline mutation
KW - human
KW - mastectomy
KW - middle aged
KW - mortality
KW - multicenter study
KW - phase 3 clinical trial
KW - randomized controlled trial
KW - tumor suppressor gene
KW - Adult
KW - Antineoplastic Agents
KW - Breast Neoplasms
KW - Chemotherapy, Adjuvant
KW - Disease-Free Survival
KW - Double-Blind Method
KW - Female
KW - Genes, BRCA1
KW - Genes, BRCA2
KW - Germ-Line Mutation
KW - Humans
KW - Mastectomy
KW - Middle Aged
KW - Phthalazines
KW - Piperazines
KW - Poly(ADP-ribose) Polymerase Inhibitors
KW - Receptor, ErbB-2
U2 - 10.1056/NEJMoa2105215
DO - 10.1056/NEJMoa2105215
M3 - Article
VL - 384
SP - 2394
EP - 2405
JO - New Engl. J. Med.
JF - New Engl. J. Med.
SN - 0028-4793
IS - 25
ER -