Effects of palbociclib and avelumab added to fulvestrant in HR+/HER2- metastatic breast cancer

Results of the PACE trial, recently published on Journal of Clinical Oncology, show a benefit in progression-free survival when palbociclib and avelumab are added to fulvestrant in HR+/HER2- metastatic breast cancer patients.

The randomized multicenter phase II PACE trial enrolled 220 patients with HR+/HER2- metastatic breast cancer whose disease had progressed on previous CDK4/6i and aromatase inhibitor therapy, to evaluate whether continuation of CDK4/6 inhibition using palbociclib with a change to fulvestrant improves outcomes over fulvestrant alone. Patients, mostly postmenopausal, were randomly assigned to receive fulvestrant, fulvestrant plus palbociclib, or fulvestrant plus palbociclib and avelumab. Results showed a median progression-free survival of 4.8 months on fulvestrant and 4.6 months on fulvestrant plus palbociclib; the median progression-free survival on fulvestrant, palbociclib and avelumab was 8.1 months. As authors say, «the PACE trial demonstrates that continuation of the same CDK4/6i beyond progression in combination with a change from aromathase inhibitor to fulvestrant does not yield a progression-free survival benefit compared with fulvestrant alone. The prolonged progression-free survival with the triplet (fulvestrant, palbociclib and avelumab) supports preclinical evidence that immune checkpoint inhibitors may produce synergistic activity with CDK4/6i in this patient population and warrants further research. The results of this trial also support the continuous investigation of predictive biomarkers for HR+/HER2– metastatic breast cancer». The difference in progression-free survival with fulvestrant and palbociclib and fulvestrant, palbociclib and avelumab versus fulvestrant was indeed greater among patients with baseline ESR1 and PIK3CA alterations. As the associate editor of JCO Gini Fleming wrote in an editorial, «Palbociclib should not be continued beyond progression. The trend toward benefit with the addition of avelumab is intriguing and should spur further research on the use of immune checkpoint inhibition in hormone receptor–positive breast cancer».