Multinational phase 3 trial of pembrolizumab and chemotherapy for high-risk, early-stage, ER-positive/HER2-negative breast cancer

The multinational phase 3 KEYNOTE-756 trial evaluated neoadjuvant pembrolizumab plus chemotherapy versus placebo plus chemotherapy, followed by surgery and adjuvant pembrolizumab plus adjuvant endocrine therapy versus placebo plus adjuvant endocrine therapy, among patients with high-risk, ER-positive/HER2-negative early-stage breast cancer (ER+ HER2- EBC). Dual primary endpoints were pathological complete response (pCR) and event-free survival (EFS). At the first interim analysis of the study, pCR rate was 24.3% (95% CI 21.0-27.8) in the pembrolizumab-chemotherapy group versus 15.6% (12.8-18.6) in the placebo-chemotherapy group (p=0.00005), with improved pCR rate with pembrolizumab in most subgroups. EFS was not mature in this analysis. The exploratory endpoint residual cancer burden also favored pembrolizumab over placebo. During the neoadjuvant phase, treatment-related adverse events of grade 3 or higher were reported in 52.5% of patients in the pembrolizumab-chemotherapy group and 46.4% of patients in the placebo-chemotherapy group. The authors conclude that addition of pembrolizumab to neoadjuvant chemotherapy significantly improved pCR rate among patients with high-risk ER+ HER2- EBC.