Emerging evidence demonstrates that the androgen-signaling pathway plays a role in BC pathogenesis and may be a valuable therapeutic target. In TBCRC011, bicalutamide (B) in patients (pts) with AR + /ER/PR- MBC was well-tolerated and demonstrated a clinical benefit rate 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/PR- MDA-MB-453 BC cells. In postmenopausal pts with luminal ER+ MBC the addition of P to letrozole significantly improved median progression-free survival (PFS) in comparison to letrozole alone. Given the luminal signature of AR+ triple negative BC (TNBC) and the presence of intact Rb in this ER(-) subtype, we are testing the efficacy of B + P in pts with metastatic AR+ TNBC. This Phase I study is evaluating the safety and PK of this drug combination and will establish the recommended phase II dose for further study. NCT02605486.
Pts with AR+ (IHC ≥ 1%)/ER any/HER2(-) MBC on central review at MSK were eligible if met following criteria: ECOG ≤2, postmenopausal, no limit to prior regimens. Pts with ER+ BC must have had 1 prior endocrine therapy. Treatment (tx): B 100 mg orally daily and P 100 mg orally daily 3 weeks on 1 week off for the 1st dose-escalation cohort (DLT period = 28 days). Pts are evaluated for toxicity every 2-4 weeks and for response every 8 weeks. Ph I standard 3 + 3 design with 3 dose escalations. Plasma for PK was collected throughout the study.
As of 5/11/16, 7 pts with AR+ MBC are enrolled. Accrual is complete to the second dose escalation cohort and the final cohort of B 150mg + P 125 mg is enrolling as of May 2016. Tx has been well tolerated: the only related Grade 3 AE was neutropenia in 1 pt. No related Grade 4 or 5 AEs were observed. One SAE of Grade 3 anemia, Grade 4 hypercalcemia was related to disease progression. PK analysis is ongoing.
The combination of palbociclib and bicalutamide has been well tolerated with no unexpected toxicity observed. Updated safety and PK data will be presented.
Clinical trial identification
Legal entity responsible for the study
A. Gucalp, T.A. Traina: Research support from Medivation, Astellas, Pfizer and Innocrin
All other authors have declared no conflicts of interest.