Multicenter randomized phase 2 trial of fulvestrant, palbociclib, and avelumab for previously treated HR-positive/HER2 negative metastatic breast cancer

CDK4/6 inhibitors have demonstrated activity in patient with HR-positive/HER2-negative metastatic breast cancer (HR+ HER2- mBC), but it is not known whether patients might derive benefit from continuation of CDK4/6 inhibitors with endocrine therapy beyond initial tumor progression or whether the addition of immune checkpoint inhibitor therapy has value in this setting. The multicenter randomized phase 2 PACE trial randomized patients with HR+ HER2- mBC whose disease progressed on a previous CDK4/6 inhibitor plus aromatase inhibitor (AI) to fulvestrant (F), fulvestrant plus palbociclib (F+P), or fulvestrant plus palbociclib plus avelumab (F+P+A). The median progression-free survival was 4.8 months on F, 4.6 months on F+P, and 8.1 months on F+P+A. The authors conclude that among patients with HR+ HER2- mBC and progression on previous CDK4/6-inhibitor plus AI, addition of palbociclib to fulvestrant did not improve PFS. The increased PFS seen with the addition of avelumab warrants further investigation.