Efficacy of Palbociclib Combinations in Hormone Receptor–Positive Metastatic Breast Cancer Patients After Prior Everolimus Treatment

This retrospective study examined outcomes of hormone receptor-positive (HR ⁺ ) human epidermal growth factor receptor 2 nonamplified (HER2 ⁻ ) metastatic breast cancer (MBC) in patients with prior exposure to everolimus on palbociclib-based therapy. Twenty-three eligible patients with HR ⁺ HER2 ⁻ MBC were assessed. Median progression-free survival (PFS) was 2.9 months (95% confidence interval, 2.1-4.2), objective response rate (ORR) 0 (0%) of 23 and clinical benefit rate (CBR) of 4 (17.4%) of 23. We found a limited clinical activity of palbociclib combinations after progression of disease in patients receiving everolimus combination. Purpose: Outcome data on hormone receptor positive (HR ⁺ ), human epidermal growth factor receptor 2 (HER2) nonamplified (HER2 ⁻ ) metastatic breast cancer (MBC) treated with palbociclib after treatment with everolimus are lacking. The PALOMA-3 trial, showing benefit of palbociclib plus fulvestrant compared to fulvestrant alone in HR ⁺ HER2 ⁻ MBC after progression while receiving endocrine therapy excluded women previously treated with everolimus. The objective of this study was to examine outcomes of HR ⁺ HER2 ⁻ MBC with prior exposure to everolimus while receiving palbociclib-based therapy. Patients and Methods: A retrospective, single-institute review was conducted of HR ⁺ HER2 ⁻ MBC from January 2014 to November 2016 in patients treated with palbociclib after prior treatment with everolimus. Progression-free survival (PFS) was defined as the time from initiation of palbociclib to the date of progression as determined by the treating physician based on radiologic, biochemical, and/or clinical criteria. Response rates were determined on the basis of available radiologic data. Objective response rate (ORR) was defined as the rate of any complete or partial responses; clinical benefit rate (CBR) was the rate of complete response, partial response, or stable disease for at least 24 weeks. Results: Twenty-three patients with a mean (range) age of 68 (42-81) years were identified. Kaplan-Meier estimate showed median PFS of 2.9 months (95% confidence interval, 2.1-4.2); ORR was 0 of 23 and CBR was 4 (17.4%) of 23. In the PALOMA-3 trial, median PFS, ORR, and CBR of palbociclib cohort were 9.5 months (95% confidence interval, 9.2-11.0), 19%, and 67%, respectively. Conclusion: There is a limited clinical activity of palbociclib combinations after progression with everolimus combination therapy. Further studies are necessary to confirm these findings.