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

Abstract

We evaluated the survival impact of adding platinum to standard taxane-anthracycline neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). 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. 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 <i>P</i> = .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 <i>P</i> = .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 <i>P</i> = .003; 5-year EFS 75.0% <i>v</i> 59.6%) and OS (HR, 0.57 [95% CI, 0.40 to 0.82]; nominal <i>P</i> = .002; 5-year OS 78.2% <i>v</i> 64.6%) were significantly higher, while in postmenopausal patients, EFS (HR, 1.19 [95% CI, 0.80 to 1.78]; nominal <i>P</i> = .386) and OS (HR, 1.06 [95% CI, 0.70 to 1.61]; nominal <i>P</i> = .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. Carboplatin did not significantly increase EFS but significantly increased the OS in patients with TNBC, with benefits confined to premenopausal patients.