Dr. Mayer on the PACE Trial in HR+/HER2– Breast Cancer

Erica L. Mayer, MD, MPH, director, Clinical Research Institute, physician, Dana-Farber Cancer Institute, associate professor of Medicine, Harvard Medical School, discusses findings from the phase 2 PACE trial (NCT03147287) in patients with hormone receptor (HR)–positive/HER2-negative metastatic breast cancer.

Investigators examined the combination of palbociclib (Ibrance) plus fulvestrant (Faslodex) vs fulvestrant alone. The trial enrolled 220 patients with HR-positive/HER2-negative metastatic breast cancer who progressed on a CDK4/6 inhibitor and endocrine therapy with at least 6 months of stable disease. Patients were not permitted to have more than 2 prior lines of endocrine therapy, and prior exposure to fulvestrant was not allowed. Patients were randomly assigned 1:2:1 to receive fulvestrant alone, palbociclib plus fulvestrant, or palbociclib plus fulvestrant and avelumab (Bavencio).

Data presented at the 2022 San Antonio Breast Cancer Symposium showed that palbociclib plus fulvestrant beyond progression on a prior CDK4/6 inhibitor did not significantly improve progression-free survival (PFS) compared with fulvestrant alone. At median follow-up of 23.6 months, findings showed that patients treated with palbociclib plus fulvestrant experienced a median PFS of 4.6 months, compared with 4.8 months for those given fulvestrant alone. Mayer notes that the majority of enrolled patients received palbociclib as their prior CDK4/6 inhibitor and had been on that regimen for more than 1 year.

Although the primary end point for the superiority of palbociclib plus fulvestrant vs fulvestrant alone was negative, findings for the secondary end point for the superiority of palbociclib plus fulvestrant and avelumab vs fulvestrant alone were hypothesis generating, Mayer says. Patients administered the triplet achieved a median PFS of 8.1 months.

The findings from the addition of the PD-L1 inhibitor avelumab presented investigators with the potential benefit of immune-oncology (IO) therapy for patients with HR-positive breast cancer, Mayer says. The ongoing evaluation of serial circulating tumor DNA and circulating tumor cell samples will allow investigators to explore of the mutational and resistance landscape, plus markers of sensitivity to IO therapy, in patients with HR-positive breast cancer.