Palbociclib Plus Fulvestrant Increases OS in HR+, HER2-Negative Breast Cancer

A recent trial sought to assess the effect of palbociclib on overall survival (OS) and the efficacy of subsequent therapy in patients with hormone receptor–positive (HR+), HER2-negative advanced breast cancer.

Hormone receptor—positive (HR+) breast cancer is the most common subtype for the disease. While it has been well documented that cyclin-dependent kinases 4 and 6 (CDK4/6) prolong progression-free survival among patients with previously untreated estrogen receptor–positive (ER+), and HER2-negative advanced breast cancer, long-term data regarding the effect of palbociclib on overall survival (OS) and the efficacy of subsequent therapy have been limited.

The PALOMA-3 trial, a prospective, international, randomized, double-blind, placebo-controlled phase 3 trial compared treatment with palbociclib plus fulvestrant with placebo plus fulvestrant in women with HR+, HER2-negative breast cancer who had disease progression after endocrine therapy.

The study enrolled 521 patients and randomized them in a 2:1 ratio to receive either palbociclib plus fulvestrant (n = 347) or placebo plus fulvestrant (n = 174). Researchers defined OS as the time from randomization to death from any cause.

Data regarding OS were analyzed at a median follow up of 44.8 months. A total of 201 deaths occurred in the palbociclib plus fulvestrant group, and 109 deaths in the placebo plus fulvestrant group. The median OS was 34.9 months (95% CI, 28.8 to 40.0) in the palbociclib plus fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo plus fulvestrant group. The estimated rate of OS at 3 years in the Kaplan—Meir analysis was 50% (95% CI, 44.0 to 55.0) in the palbociclib­ plus fulvestrant group and 41% (95% CI, 33.0 to 48.0) in the placebo­ plus fulvestrant group. Additionally, the safety profile of palbociclib plus fulvestrant remained consistent with that in the primary analysis.

The results of the analysis did not meet the prespecified threshold for statistical significance, but the addition of palbociclib to fulvestrant resulted in “an absolute prolongation of overall survival of 6.9 months among patients with HR+, HER2-negative advanced breast cancer.” The study authors also noted that in the subgroup of patients with sensitivity to previous endocrine therapy, OS was 10 months longer with palbociclib plus fulvestrant than with placebo.


Turner N, Slamon D, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer [published online October 20, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1810527