Palbociclib and Letrozole in Advanced Breast Cancer
Mené sur 666 patientes atteintes d'un cancer du sein ER+/HER2- de stade avancé après la ménopause, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement de première ligne combinant palbociclib et létrozole
Background : A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication.
Methods : In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety.
Results : The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib–letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo–letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib–letrozole group vs. 1.4% in the placebo–letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib–letrozole group and in none of the patients in the placebo–letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib–letrozole group and in 13 patients (5.9%) in the placebo–letrozole group.
Conclusions : Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib combined with letrozole resulted in significantly longer progression-free survival than that with letrozole alone, although the rates of myelotoxic effects were higher with palbociclib–letrozole. (Funded by Pfizer; PALOMA-2 ClinicalTrials.gov number, NCT01740427.)
New England Journal of Medicine , résumé, 2015