Turner NC, et al. - As patients with hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer display prolongation of progression-free survival with the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, researchers sought to report the results of a prespecified analysis of overall survival. Compared to treatment with placebo–fulvestrant, treatment with palbociclib–fulvestrant resulted in longer overall survival among patients who had sensitivity to previous endocrine therapy. No significant differences in overall survival were evident in the entire trial group.

Methods

• Patients with hormone-receptor–positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy were randomized to receive palbociclib plus fulvestrant or placebo plus fulvestrant.
• Outcomes assessed included overall survival; palbociclib effect 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

• Randomization was done of 521 patients; the palbociclib–fulvestrant group displayed the median overall survival of 34.9 months (95% confidence interval [CI], 28.8 to 40.0) and the placebo–fulvestrant group had the median overall survival of 28.0 months (95% CI, 23.6 to 34.6) (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute difference, 6.9 months).
• After the completion of the trial regimen, CDK4/6 inhibitor treatment was provided to 16% of the patients in the placebo–fulvestrant group.
• Among 410 patients with sensitivity to previous endocrine therapy, the palbociclib–fulvestrant group and the placebo–fulvestrant group had the median overall survival of 39.7 months (95% CI, 34.8 to 45.7) and 29.7 months (95% CI, 23.8 to 37.9), respectively (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months).
• The two groups were similar regarding the median duration of subsequent therapy, and the palbociclib–fulvestrant group received chemotherapy for a median time of 17.6 months, 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).
• Researchers identified no new safety signals with 44.8 months of follow-up.