As reported in the Journal of Clinical Oncology by Dennis J. Slamon, MD, PhD, and colleagues, the phase III PALOMA-2 trial showed no overall survival benefit with the addition of palbociclib to letrozole in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer with no prior systemic treatment for advanced disease.
The confirmatory trial supported the March 2017 conversion of accelerated to regular approval for palbociclib plus an antihormonal agent in this setting on the basis of improved progression-free survival.
Dennis J. Slamon, MD, PhD
Study Details
In the trial, 666 patients were randomly assigned 2:1 to receive palbociclib plus letrozole (n = 444) or placebo plus letrozole (n = 222).
Key Findings
After a median follow-up of 90.1 months, 405 patients were known to have died and 155 patients were known to be alive. Median overall survival was 53.9 months (95% confidence interval [CI] = 49.8–60.8 months) in the palbociclib/letrozole group vs 51.2 months (95% CI = 43.7–58.9 months) in the control group (hazard ratio [HR] = 0.96, 95% CI = 0.78–1.18, P = .34). However, interpretation of these overall survival data was limited due to an imbalance between groups with unknown survival outcomes (13.3% vs 21.2%).
Recovery of survival data reduced the proportions of patients with unknown survival outcomes to 9.2% vs 11.7%. Analysis with recovered data yielded a median overall survival of 53.8 months (95% CI = 49.8–59.2 months) in the palbociclib group vs 49.8 months (95% CI = 42.3–56.4 months) in the control group (HR = 0.92, 95% CI = 0.76–1.12, P = .21).
A total of 399 patients (89.9%) in the palbociclib/letrozole group and 217 (97.7%) in the control group discontinued study treatment. Of these, 322 (80.7%) and 190 (87.6%) received at least one poststudy systemic therapy. Of the 399 and 217 patients who discontinued treatment, respectively, 262 (65.7%) and 161 (74.2%) patients received endocrine therapy, 221 (55.4%) and 134 (61.8%) received chemotherapy, and 47 (11.8%) and 58 (26.7%) received a CDK4/6 inhibitor.
The investigators concluded, “Overall survival was not significantly improved with palbociclib plus letrozole compared with placebo plus letrozole.”
Dr. Slamon, of the David Geffen School of Medicine, University of California Los Angeles, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Pfizer Inc. For full disclosures of the study authors, visit ascopubs.org.
