Phase I/II trial of palbociclib in combination with bicalutamide for the treatment of androgen receptor (AR)+ metastatic breast cancer (MBC)

TPS1103Background: Patients (pts) with triple negative breast cancer (TNBC) have limited effective therapeutic options and generally experience a more aggressive clinical course. Emerging evidence demonstrates that the androgen-signaling pathway plays a role in BC pathogenesis and may be a valuable therapeutic target. In TBCRC011, we tested the efficacy of the AR antagonist, bicalutamide (B) in pts with AR+/ER/PgR- MBC. B was well-tolerated and demonstrated a clinical benefit rate (CBR) of 19% in this population (Gucalp et al. CCR 2013). Palbociclib (P) is a competitive inhibitor of CDK4/6 and has been shown to reduce growth of AR+/ER/PgR- MDA-MB-453 BC cells via reduced Rb phosphorylation. In postmenopausal pts with luminal ER+ MBC the addition of P to letrozole significantly improved median progression-free survival (PFS) in comparison to letrozole monotherapy. Given the luminal signature of AR+ TNBC and the presence of intact Rb in this ER(-) subtype, we are testing the efficacy of B+P in pts with meta...