A randomized phase II study of PD 0332991, cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with letrozole for first-line treatment of patients with postmenopausal, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.

TPS100 Background: PD 0332991 is an orally bioavailable selective inhibitor of CDK4/6 and prevents cellular DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase. Preclinical evaluations suggest that reduction in CDKN2A (p16) expression and cyclin D1 (CCND1) overexpression confer susceptibility to PD 0332991 (Finn et al. Breast Cancer Res 2009;11:R77). In addition, PD 0332991 was synergistic in combination with tamoxifen in vitro in ER+ human breast cancer cell lines (Ibid.). Based on these observations, a phase I/II study (ClinicalTrials.gov ID: NCT00721409) in combination with letrozole as first-line therapy in advanced ER+ post-menopausal breast cancer was initiated. The phase I portion has been completed and the recommended phase II dose (RP2D) was determined to be PD 0332991 125 mg once daily (QD) on Schedule 3/1 (3 weeks on treatment followed by 1 week off treatment) plus letrozole 2.5 mg QD. The combination was generally well tolerated, and encouraging antitumor activity was...