Pooled analysis of addition of carboplatin to neoadjuvant chemotherapy in early-stage triple-negative breast cancer

Pooled analysis of three randomized clinical trials (BrighTNess, CALGB 40603, and GeparSixto) was carried out to better characterize the therapeutic benefits of the addition of carboplatin to anthracyline- and taxane-based neoadjuvant chemotherapy (NACT) in early-stage triple-negative breast cancer (TNBC). In the pooled data set of 1084 patients, the addition of carboplatin to NACT was associated with a higher pathologic complete response (pCR) rate (OR 1.89; 95% CI 1.41-2.55; p<0.001) and improved event-free survival (EFS: HR 0.71; 95% CI 9.54-0.93), but not overall survival (OS). Among patients with germline BRCA mutations (n=137), addition of carboplatin to NACT conveyed a significant EFS benefit but no signficant pCR rate or OS benefit. There were 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 the combined data set, PAM50 luminal and MDACC/BCM luminal androgen receptor molecular subtypes were significantly associated with lower pCR rates. The authors conclude that these findings support the addition of carboplatin to NACT within the standard-of-care treatment of stage II and III TNBC and emphasize the importance of the TNBC immune microenvironments for patient outcomes.