BACKGROUND
The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients
with hormone-receptor–positive, human epidermal growth factor receptor 2
(HER2)–negative advanced breast cancer. We report the results of a prespecified
analysis of overall survival.
METHODS
We randomly assigned patients with hormone-receptor–positive, HER2-negative
advanced breast cancer who had progression or relapse during previous endocrine
therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified
stratification factors of presence or absence of sensitivity to endocrine therapy,
presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety.
RESULTS
Among 521 patients who underwent randomization, the median overall survival
was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclib–
fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo–fulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute
difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the
trial regimen occurred in 16% of the patients in the placebo–fulvestrant group.
Among 410 patients with sensitivity to previous endocrine therapy, the median
overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclib–fulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placebo–fulvestrant
group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months).
The median duration of subsequent therapy was similar in the two groups, and
the median time to the receipt of chemotherapy was 17.6 months in the palbociclib–
fulvestrant group, as compared with 8.8 months in the placebo–fulvestrant group
(hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were
observed with 44.8 months of follow-up.
CONCLUSIONS
Among patients with hormone-receptor–positive, HER2-negative advanced breast
cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib–fulvestrant resulted in longer overall survival than treatment with placebo–
fulvestrant. The differences in overall survival in the entire trial group were not
significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135.
