Multicenter Bayesian adaptive randomized phase 2 trial of metronomic chemotherapy plus anti-PD-1 for HER2-negative metastatic breast cancer

A multicenter phase 2 clinical trial in China compared activity of metronomic chemotherapy plus PD-1 blockade versus conventional chemotherapy plus PD-1 blockade using Bayesian adaptive randomization and efficacy monitoring. Eligible patients had HER2-negative metastatic breast cancer (mBC) and had not received more than one prior line of standard chemotherapy. Patients (n=97) were randomized to (1) metronomic vinorelbine (NVB) monotherapy, (2) NVB plus toripalimab, (3) bevacizumab plus NVB and toripalimab, (4) conventional cisplatin plus NVB and toripalimab, or (5) metronomic cyclophosphamide, capecitabine, NVB, and toripalimab (VEX cohort). The primary end point was disease control rate (DCR). The VEX (69.7) and cisplatin (73.7%) cohorts had the highest DCR. The median progression-free survival was longest in the VEX cohort (6.6 months), followed by the bevacizumab (4.0 months) and cisplatin (3.5 months) cohorts. In general, the five regimens were well tolerated, with nausea and neutropenia being the most common adverse events. The authors conclude that metronomic VEX chemotherapy combined with PD-1 blockade can be a treatment option in patients with HER2-negative mBC.