DOI: 10.1200/oa-26-00101 ISSN: 2994-9750

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

Brooke M. Felsheim, Jens Huober, Lisa A. Carey, Valentina Nekljudova, Thomas Karn, Sara M. Tolaney, Andreas Schneeweiss, Michael Untch, Christoph Salat, Charles S. Kuzma, Aranzazu Fernandez-Martinez, Sivaramakrishna Rachakonda, Jose J. Ponce-Lorenzo, Dirk-Michael Zahm, Rama Suresh, Daniel G. Stover, Priya Rastogi, Maren Darsow, Diana E. Lake, Hope S. Rugo, Joyce O'Shaughnessy, Mehra Golshan, Adam D. Pfefferle, William M. Sikov, Otto Metzger, Carsten Denkert, Charles E. Geyer, Charles M. Perou, Sibylle Loibl
Show PDF Cite

Purpose

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 (ClinicalTrials.gov identifier: NCT02032277 ), Cancer and Leukemia Group B 40603 (ClinicalTrials.gov identifier: NCT00861705 ), and GeparSixto (ClinicalTrials.gov identifier: NCT01426880 ).

Methods

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 (g BRCA ) mutation status, eight gene expression signatures, and molecular subtypes (PAM50, MD Anderson Cancer Center/Baylor College of Medicine [MDACC/BCM]).

Results

In the pooled data set, the addition of carboplatin to NACT was associated with a higher pCR rate (odds ratio, 1.89 [95% CI, 1.41 to 2.55]; P < .001) and improved EFS (hazard ratio, 0.71 [95% CI, 0.54 to 0.93]; P = .01), but not OS. In patients with g BRCA 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. In addition, we found that the PAM50 luminal and MDACC/BCM luminal androgen receptor molecular subtypes were significantly associated with lower pCR rates in the combined data set.

Conclusion

Our findings support the recent addition of carboplatin to NACT within the standard-of-care treatment of stage II to III TNBC and emphasize the importance of the TNBC immune microenvironment to patient outcomes.

More from our Archive