A phase II trial of an oral CDK 4/6 inhibitor, PD0332991, in advanced breast cancer.

519 Background: The G1/S checkpoint of the cell cycle is frequently dysregulated in breast cancer (BC). Initial efficacy of PD0332991, a potent oral inhibitor of cyclin-dependent kinases (CDKs) 4/6 was shown in a variety of solid tumors and in combination with letrozole in a randomized phase II trial. Methods: We performed a phase II, single arm trial of PD0332991 in women with advanced BC. The primary objectives were safety and efficacy. Eligible patients had histologically-confirmed, stage IV BC with primary or metastatic tumor positive for retinoblastoma (Rb) protein expression, measureable disease by RECIST and adequate organ function/performance status. PD0332991 was given at 125 mg orally, days 1 – 21 of a 28-day cycle. Tumor was assessed every 2 cycles. A two-stage statistical design was employed. Secondary objectives included predictive biomarker assessment. Results: 36 patients were enrolled; 28 who completed cycle 1 are reported: 18 (64%) HR+/Her2-, 2 (7%) HR+/Her2+ and 8 (29%) HR-/Her2-. 90% ha...