[HTML][HTML] Palbociclib and letrozole in advanced breast cancer

RS Finn, M Martin, HS Rugo, S Jones… - New England journal …, 2016 - Mass Medical Soc
RS Finn, M Martin, HS Rugo, S Jones, SA Im, K Gelmon, N Harbeck, ON Lipatov, JM Walshe…
New England journal of medicine, 2016Mass Medical Soc
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 …
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.)
The New England Journal Of Medicine