@article{18a39aa1e88443559652480e6f8b0d70,
title = "Long-term efficacy and safety of addition of carboplatin with or without veliparib to standard neoadjuvant chemotherapy in triple-negative breast cancer: 4-year follow-up data from BrighTNess, a randomized phase III trial",
abstract = "Background: Primary analyses of the phase III BrighTNess trial showed addition of carboplatin with/without veliparib to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates with manageable acute toxicity in patients with triple-negative breast cancer (TNBC). Here, we report 4.5-year follow-up data from the trial. Patients and methods: Women with untreated stage II-III TNBC were randomized (2 : 1 : 1) to paclitaxel (weekly for 12 doses) plus: (i) carboplatin (every 3 weeks for four cycles) plus veliparib (twice daily); (ii) carboplatin plus veliparib placebo; or (iii) carboplatin placebo plus veliparib placebo. All patients then received doxorubicin and cyclophosphamide every 2-3 weeks for four cycles. The primary endpoint was pCR. Secondary endpoints included event-free survival (EFS), overall survival (OS), and safety. Since the co-primary endpoint of increased pCR with carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel was not met, secondary analyses are descriptive. Results: Of 634 patients, 316 were randomized to carboplatin plus veliparib with paclitaxel, 160 to carboplatin with paclitaxel, and 158 to paclitaxel. With median follow-up of 4.5 years, the hazard ratio for EFS for carboplatin plus veliparib with paclitaxel versus paclitaxel was 0.63 [95% confidence interval (CI) 0.43-0.92, P = 0.02], but 1.12 (95% CI 0.72-1.72, P = 0.62) for carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel. In post hoc analysis, the hazard ratio for EFS was 0.57 (95% CI 0.36-0.91, P = 0.02) for carboplatin with paclitaxel versus paclitaxel. OS did not differ significantly between treatment arms, nor did rates of myelodysplastic syndromes, acute myeloid leukemia, or other secondary malignancies. Conclusions: Improvement in pCR with the addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without increasing the risk of second malignancies, whereas adding veliparib did not impact EFS. These findings support the addition of carboplatin to weekly paclitaxel followed by doxorubicin and cyclophosphamide neoadjuvant chemotherapy for early-stage TNBC.",
keywords = "carboplatin, neoadjuvant chemotherapy, phase III, triple-negative breast cancer, veliparib",
author = "Geyer, {C. E.} and Sikov, {W. M.} and J. Huober and Rugo, {H. S.} and N. Wolmark and J. O'Shaughnessy and D. Maag and M. Untch and M. Golshan and Lorenzo, {J. Ponce} and O. Metzger and M. Dunbar and Symmans, {W. F.} and P. Rastogi and Sohn, {J. H.} and R. Young and Wright, {G. S.} and C. Harkness and K. McIntyre and D. Yardley and S. Loibl",
note = "Funding Information: Medical writing support was provided by Chun Zhou of Fishawack Communications, Ltd. This work was supported by AbbVie (no grant number). AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data and in the writing, reviewing, and approval of the manuscript. All authors had access to all relevant data and participated in writing, review, and approval of this manuscript, with editorial assistance funded by the study funder. No honoraria or payments were made for authorship. CEG received travel funding from Genentech, Roche, Daiichi Sankyo, and AstraZeneca; has received writing support from Roche and AbbVie; has been on uncompensated advisory boards for Genentech, Roche, Daiichi Sankyo, and Seattle Genetics; has been on compensated advisory boards for Exact Sciences; has an uncompensated consulting role for Daiichi Sankyo; and has a compensated consulting role for Athenex. WMS is an unpaid member of the Steering Committee for AbbVie. JH received research funding from Celgene, Hexal, and Novartis; received honoraria from AbbVie, AstraZeneca, Celgene, Eisai, Gilead, Lilly, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, and Seagen; has a consulting and advisory role for AbbVie, AstraZeneca, Celgene, Lilly, Hexal, MSD, Novartis, and Roche; reports travel expenses from Celgene, Daiichi, Novartis, Pfizer, and Roche. HSR received research support for clinical trials through the University of California from AstraZeneca, Boehringer Ingelheim, Daiichi, Genentech, Immunomedics, Lilly, Macrogenics, Merck, Novartis, Odonate, Pfizer, Polyphor, Seattle Genetics, and Sermonix; received honoraria from Mylan, Puma, and Samsung. JO received honoraria for consulting and/or advisory boards from AbbVie, Agendia, and Amgen Biotechnology, Aptitude Health, AstraZeneca, Bayer, Bristol Myers Squibb (BMS), Celgene Corporation, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Gilead Sciences, GRAIL, Halozyme Therapeutics, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Pierre Fabre Pharmaceuticals, Prime Oncology, Puma Biotechnology, Roche, Samsung Bioepis, Sanofi, Seagen, Syndax Pharmaceuticals, Taiho Oncology, Takeda, and Synthon. DM and MD are AbbVie employees and may hold stock or options. MU is on lectures and advisory boards for AbbVie, Agendia, Amgen, AstraZeneca, BioNTech, BMS, Celgene, Daiichi Sankyo, Eisai, GlaxoSmithKline (GSK), Jansen Cilag, Johnson & Johnson, Lilly, Molecular Health, MSD, Mundipharma, Myriad, Novartis, Pfizer, Pierre Fabre, Roche, and Seagen; has a consulting role for AbbVie. MG is an unpaid member of the Steering Committee for AbbVie. JPL received honoraria for consulting and/or advisory boards from Novartis, Pfizer, AstraZeneca, Lilly, and Roche. OM received consulting fee from AbbVie and G1 Therapeutics; received research funding from AbbVie, Genentech, Pfizer, and Roche; reports travel expenses from AbbVie and Grupo Oncoclinicas; is uncompensated co-chair of advisory board for Pfizer. WFS holds founder shares from Delphi Diagnostics; has intellectual property from Delphi Diagnostics; holds public company shares from Eiger Biopharmaceuticals and IONIS Pharmaceuticals; is on compensated advisory board for Merck; is on uncompensated advisory boards for Delphi Diagnostics and Roche. PR reports unpaid advisory boards, travel, and accommodations from Genentech/Roche; reports travel and accommodations from Lilly and AstraZeneca. JHS received research funding from MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, and Boehringer Ingelheim. RY is on Speakers bureau for Genentech. GSW received grants or contracts from AbbVie, Astellas, AstraZeneca, Roche, Innocrine Pharm, H3BioMedicine Inc. G1 Therapeutics, Daiichi Sankyo, Sermonix Pharm, Taiho Oncology, Seattle Genetics, Inc. Immunogen, Incyte, Genentech, Novartis, Lilly, Janssen, Celgene, Bristol Myers Squibb, Boehringer Ingelheim, Medivation, Macrogenics, Merrimack, Tesaro, and Pfizer. DY has a consulting or advisory role for Novartis, Biotheranostics, Bristol Myers Squibb, G1 Therapeutics, Athenex, Immunomedics, Sanofi/Aventis, R-Pharm, Lilly; is on speakers bureau for Novartis and Genentech/Roche; received research funding from Genentech/Roche, Novartis, MedImmune, Lilly, Medivation, Pfizer, Tesaro, Macrogenics, AbbVie, Merck, Clovis Oncology, Amgen, Biomarin, Biothera, Dana Farber Cancer Hospital, Incyte, Innocrin Pharma, Nektar, NSABP Foundation, Odonate Therapeutics, Polyphor; reports travel expenses from Novartis and Genentech/Roche. SL reports grant paid to from AbbVie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Immunomedics/Gilead, Novartis, Pfizer, Roche, and Vifor; received honorarium for advisory boards paid to institute: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Daiichi Sankyo, Eirgenix, GSK, Lilly, Merck KG, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Puma, Roche, and Seagen; is on lectures paid to institute for Chugai (personal), Daiichi Sankyo, Novartis, Pfizer, Pierre Fabre, PriME/Medscape, Roche, and Samsung; has a medical writing role for AbbVie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Novartis, Pfizer, and Roche. All other authors have declared no conflicts of interest. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis datasets), as well as other information (e.g. protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement. Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html. Funding Information: This work was supported by AbbVie (no grant number). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = apr,
doi = "10.1016/j.annonc.2022.01.009",
language = "English (US)",
volume = "33",
pages = "384--394",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "4",
}