Phase III PALOMA-3 trial of Ibrance + fulvestrant misses statistical significance in overall survival in metastatic breast cancer.- Pfizer.

Pfizer announced overall survival (OS) results from the Phase III PALOMA-3 trial, which evaluated Ibrance (palbociclib) in combination with fulvestrant compared to placebo plus fulvestrant in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer whose disease has progressed after prior endocrine therapy.

The results demonstrated a positive trend in the hazard ratio favoring the Ibrance combination, although this trend did not reach statistical significance. Overall survival is a secondary endpoint of the PALOMA-3 trial and, as such, the trial design was not optimized to detect a statistically significant difference in OS. PALOMA-3 met its primary endpoint of progression-free survival (PFS) at interim analysis and results were published in The New England Journal of Medicine in June 2015; updated PFS data were later presented at the 2016 San Antonio Breast Cancer Symposium. The trial demonstrated a statistically significant and clinically meaningful improvement in PFS for Ibrance plus fulvestrant compared to placebo plus fulvestrant. The most common adverse reactions in PALOMA-3 included neutropenia, leukopenia, infections, fatigue and nausea; no new safety signals were identified as part of this final OS analysis.

Comment: PFS is a well-established measure of clinical benefit in metastatic breast cancer trials. Ibrance in combination with fulvestrant has been approved in more than 80 countries around the world based on the PFS demonstrated in PALOMA-3.