Palbociclib in combination with letrozole as first-line treatment for advanced breast cancer: A Japanese phase II study.

This single-arm, open-label, phase II study in 42 Japanese postmenopausal patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week off) coadministered with letrozole (2.5 mg once daily). Primary endpoint of investigator-assessed 1-year progression-free survival (PFS) probability was 75.0% (90% CI, 61.3%-84.4%), far surpassing the 40% lower limit of the 90% CI supporting efficacy. Median duration of treatment was 438 days. Among secondary efficacy measures, median PFS was not reached (95% CI, 16.7: not estimable), 17/42 patients (40.5%) had an objective response, 36/42 (85.7%) maintained disease control, and 27/42 (64.3%) remained in follow-up. Median overall survival was not reached, and 1-year survival probability was 92.9% (95% CI, 79.5%-97.6%). Results of intensive pharmacokinetics in a subset of 6 patients showed palbociclib steady-state mean area under the plasma concentration-time curve over the dosing interval [τ] and mean maximum plasma concentration were 1979 ng·h/mL and 124.7 ng/mL, respectively. For day 15 plasma samples from cycles 1 and 2, geometric mean of the within-patient mean trough concentration was 90.1 ng/mL. The most common treatment-related adverse events were neutropenia (100%) and stomatitis (73.8%). There was 1 case of treatment-related febrile neutropenia. Toxicities were generally tolerated and manageable by dose modifications and/or medical care. Efficacy and safety of first-line palbociclib plus letrozole therapy is supported in Japanese postmenopausal patients with treatment-naive ER+/HER2- advanced breast cancer.