In the phase II PACE trial reported in the Journal of Clinical Oncology, Erica L. Mayer, MD, MPH, and colleagues found no improvement in progression-free survival with the addition of palbociclib to fulvestrant—but a numeric improvement with the further addition of avelumab—in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer whose disease progressed on prior CDK4/6 inhibitor and aromatase inhibitor treatment.
Erica L. Mayer, MD, MPH
Study Details
In the U.S. multicenter open-label trial, 220 patients were randomly assigned 1:2:1 between September 2017 and February 2022 to receive fulvestrant (n = 55), fulvestrant/palbociclib (n = 111), or fulvestrant/palbociclib/avelumab (n = 54). All treatments were given in 28-day cycles: fulvestrant at 500 mg was given on days 1 and 15 in cycle 1 and on day 1 of each subsequent cycle; palbociclib at 125 mg was given once daily on days 1 to 21 of each cycle; and avelumab at 10 mg/kg was given every 14 days. The primary endpoint was investigator-assessed progression-free survival in the fulvestrant/palbociclib group vs the fulvestrant group.
Key Findings
Median follow-up was 23.6 months. Median progression-free survival was 4.6 months (90% confidence interval [CI] = 3.6–5.9 months) in the fulvestrant/palbociclib group vs 4.8 months (90% CI = 2.1–8.2 months) in the fulvestrant group (hazard ratio [HR] = 1.11, 90% CI = 0.79–1.55, P = .62). Median progression-free survival in the fulvestrant/palbociclib/avelumab group was 8.1 months (90% CI = 3.2–10.7 months), with a hazard ratio vs the fulvestrant group of 0.75 (90% CI = 0.50–1.12, P = .23).
Among patients with baseline ESR1 alterations, median progression-free survival was 5.2 months in the fulvestrant/palbociclib group vs 3.3 months in the fulvestrant group (HR = 0.68, 90% CI = 0.42–1.09). Among patients with baseline PIK3CA alterations, median progression-free survival was 4.6 months vs 2.0 months (HR = 0.56, 90% CI = 0.32–0.99).
Median overall survival was 24.6 months in the fulvestrant/palbociclib group vs 27.5 months in the fulvestrant group (HR = 1.02, 90% CI = 0.67–1.56). Median overall survival in the fulvestrant/palbociclib/avelumab group was 42.5 months (HR vs fulvestrant group = 0.68, 90% CI = 0.40–1.15).
Grade 3 or 4 treatment-related adverse events occurred in 1.9% of the fulvestrant group, 41.8% of the fulvestrant/palbociclib group, and 68.9% of the fulvestrant/palbociclib/avelumab group. The most common treatment-related adverse events of any grade in the three groups were, respectively: fatigue (34.0%); neutropenia (65.5%, 32.7% grade 3–4), fatigue (34.5%), and anemia (21.8%); and neutropenia (73.6%, 49.1% grade 3–4), fatigue (64.2%), anemia (34.0%), and thrombocytopenia (32.1%). No treatment-related deaths were reported.
The investigators concluded, “The addition of palbociclib to fulvestrant did not improve progression-free survival vs fulvestrant alone among patients with HR-positive/HER2-negative metastatic breast cancer whose disease had progressed on a previous CDK4/6 inhibitor plus aromatase inhibitor. The increased progression-free survival seen with the addition of avelumab warrants further investigation in this patient population.”
Dr. Mayer, of the Department of Medical Oncology, Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Pfizer and others. For full disclosures of the study authors, visit ascopubs.org.
