Addition of Carboplatin to Sequential Taxane-Anthracycline Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer: A Phase III Randomized Controlled Trial.

PURPOSE: We evaluated the survival impact of adding platinum to standard taxane-anthracycline neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). METHODS: In this phase III trial, patients with TNBC were randomly assigned, after stratification by stage and menopausal status, to receive neoadjuvant chemotherapy comprising once-per-week carboplatin (AUC-2) plus paclitaxel (100 mg/m2) for 8 weeks, followed by four cycles of anthracycline plus cyclophosphamide, or same chemotherapy without carboplatin. The primary end point was event-free survival (EFS), and secondary end points were overall survival (OS) and pathologic complete response. This is the prespecified primary analysis of this study. RESULTS: Of 720 patients randomly assigned between April 2010 and January 2020, 717 (platinum 361, control 356) were included in modified intention-to-treat analysis. At median follow-up of 67.6 months, in platinum and control arms, there were 111/361 and 131/356 EFS events (hazard ratio [HR], 0.80 [95% CI, 0.62 to 1.03]; two-sided unstratified P = .081), with 5-year EFS of 70.7% (95% CI, 65.8% to 75.6%) and 64.1% (95% CI, 59.0% to 69.2%), respectively, and 94/361 and 121/356 deaths (HR, 0.74 [95% CI, 0.57 to 0.97]; nominal P = .029), with 5-year OS of 74.4% and 66.8%, respectively. In premenopausal patients, EFS (HR, 0.61 [95% CI, 0.43 to 0.84]; nominal P = .003; 5-year EFS 75.0% v 59.6%) and OS (HR, 0.57 [95% CI, 0.40 to 0.82]; nominal P = .002; 5-year OS 78.2% v 64.6%) were significantly higher, while in postmenopausal patients, EFS (HR, 1.19 [95% CI, 0.80 to 1.78]; nominal P = .386) and OS (HR, 1.06 [95% CI, 0.70 to 1.61]; nominal P = .772) were not significantly different, in platinum versus control arm. There was statistically significant interaction between study intervention and menopausal status for EFS and OS, with a benefit of adding platinum in premenopausal but not in postmenopausal patients. There was more grade ≥3 myelosuppression in carboplatin arm, but there was no difference in nonhematologic toxicities. CONCLUSION: Carboplatin did not significantly increase EFS but significantly increased the OS in patients with TNBC, with benefits confined to premenopausal patients.