A Randomized Phase Ii Study Of Androgen Deprivation Therapy With Or Without Pd0332991 In Rb-Positive Metastatic Hormone-Sensitive Prostate Cancer.

TPS5074 Background: Androgens drive proliferation of prostate cancer cells via upregulation of cyclin D which complexes with the CDK4/6 kinases, resulting in phosphorylation of Rb and G1/S progression. Perturbations in this pathway (loss of Rb, upregulation of cyclin D) are felt to promote castration-resistance. PD0332991 (palbociclib) is a novel specific inhibitor of CDK4 and 6. Preclinically PD0332991 inhibited proliferation and promoted G1 arrest in an RB and Cyclin D-dependent manner. 80-90% of early metastatic hormone-sensitive prostate cancers are estimated to retain wild-type RB expression. Addition of PD0332991 to hormonal therapy in ER+ breast tumors demonstrated statistically significant improvements in progression-free survival. Hypothesis: Addition of PD0332991 to initial ADT in patients with newly metastatic RB-positive prostate cancer will significantly increase the efficacy of ADT. Methods: A multicenter randomized phase II study of PD0332991 was initiated (NCT02059213) in which patients (n...