Journal Article

DKFZ-2026-02770

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Impact of Neoadjuvant Carboplatin in Early-Stage Triple-Negative Breast Cancer: A Pooled Analysis of the BrighTNess, Cancer and Leukemia Group B 40603 (Alliance), and GeparSixto Clinical Trials.

Felsheim, B. M. ; Huober, J. ; Carey, L. A. ; Nekljudova, V. ; Karn, T. ; Tolaney, S. M. ; Schneeweiss, A.DKFZ* ; Untch, M. ; Salat, C. ; Kuzma, C. S. ; Fernandez-Martinez, A. ; Rachakonda, S. ; Ponce-Lorenzo, J. J. ; Zahm, D.-M. ; Suresh, R. ; Stover, D. G. ; Rastogi, P. ; Darsow, M. ; Lake, D. E. ; Rugo, H. S. ; O'Shaughnessy, J. ; Golshan, M. ; Pfefferle, A. D. ; Sikov, W. M. ; Metzger, O. ; Denkert, C. ; Geyer, C. E. ; Perou, C. M. ; Loibl, S.

2026

Abstract: To better characterize the therapeutic benefits of the addition of carboplatin to anthracycline- and taxane-based neoadjuvant chemotherapy (NACT) in early-stage triple-negative breast cancer (TNBC), we performed a pooled analysis of three randomized clinical trials: BrighTNess (NCT02032277), CALGB 40603 (NCT00861705), and GeparSixto (NCT01426880).We evaluated the impact of the addition of carboplatin to NACT on pathologic complete response (pCR) rates, event-free survival (EFS), and overall survival (OS) across a combined total of 1,084 patients. We additionally looked for associations of outcome by germline BRCA1 and BRCA2 (gBRCA) mutation status, eight gene expression signatures, and molecular subtypes (PAM50, MDACC/BCM).In the pooled dataset, the addition of carboplatin to NACT was associated with a higher pCR rate (odds ratio = 1.89, 95% confidence interval [CI] = 1.41-2.55, p < 0.001) and improved EFS (hazard ratio = 0.71, 95% CI = 0.54-0.93, p = 0.01), but not OS. In patients with gBRCA mutations (n = 137), we found that the addition of carboplatin conveys a significant EFS benefit but had no significant association with pCR rate or OS. We found six immune gene expression signatures that were significantly associated with a higher pCR rate and four that were significantly associated with improved EFS and OS. Additionally, we found that the PAM50 luminal and MDACC/BCM LAR molecular subtypes were significantly associated with lower pCR rates in the combined dataset.Our findings support the recent addition of carboplatin to NACT within the standard of care treatment of stage II-III TNBC and emphasize the importance of the TNBC immune microenvironment to patient outcomes.

Note: #NCTZFB26# / Missing Journal: JCO Oncology Advances (JCO Oncol Adv) = 2994-9750 (import from CrossRef, PubMed, , Journals: inrepo02.dkfz.de)

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Contributing Institute(s):

1. Koordinierungsstelle NCT Heidelberg (HD02)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

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