Results of a randomized phase 2 study of PD 0332991, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with letrozole vs letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (BC)

SUMMARY: PD 0332991 is an oral,  selective inhibitor of CDK4/6 kinases. This agent interrupts cellular DNA synthesis  by inhibiting the progression of the cell cycle from G1 to S phase and thus prevents tumor cell growth. The results presented, includes the pooled data from the study of  2 cohorts of patients. Both groups included postmenopausal women with advanced breast cancer and  ER positive, HER2 negative tumors. Patients were randomized 1:1 to receive either letrozole (FEMARA®)  along with PD 0332991 or FEMARA® alone. Group 1 enrolled 66 patients and Group 2 enrolled 99 patients. Group 2 patient tumors  were also  evaluated  for the biomarkers cyclinD1 amplification and/or loss of p16, by FISH analysis. For both these study groups, the primary endpoint was Progression Free Survival (PFS). Secondary endpoints included response rates, overall survival, safety, and biomarker correlates. Data from the pooled analysis which included 165 women from both the groups demonstrated a median PFS of 26.1 months for the combination compared to 7.5 months with FEMARA® alone. This represented a 63% reduction in risk of progression  (hazard ratio =0.37; P < 001). The most common adverse events noted in the combination group included uncomplicated neutropenia, anemia, and fatigue. Biomarkers expression (cyclinD1 amplification and/or loss of p16) had no impact on outcomes suggesting  that the biomarker for PD0332991 may be the estrogen receptor itself rather than CDK4/6 kinases. Finn RS, Crown JP, Lang I, et al. CTRC-AACR San Antonio Breast Cancer Symposium 2012; Abstract S1-6.