A Randomized Phase II Study of Androgen Deprivation Therapy with or without Palbociclib in RB-positive Metastatic Hormone Sensitive Prostate Cancer (mHSPC).

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Clinical cancer research : an official journal of the American Association for Cancer Research


california; jwci


PURPOSE: We hypothesized that co-targeting AR and cell-cycle with palbociclib (a CDK4/6 inhibitor) would improve outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

EXPERIMENTAL DESIGN: 60 patients with Rb-intact mHSPC were randomized (1:2) to Arm 1: androgen deprivation (AD) or Arm 2: AD+ palbociclib. The primary endpoint was PSA response rate (RR) after 28-weeks of therapy. Secondary endpoints included safety, PSA and clinical progression-free survival (PFS), PSA and radiographic RR. Tumors underwent exome sequencing when available. Circulating tumor cells (CTC) were enumerated at various time points.

RESULTS: 72 patients with mHSPC underwent metastatic disease biopsy and 64 had adequate tissue for RB assessment. 62/64 (97%) retained RB expression. 60 patients initiated therapy (Arm 1: 20; Arm 2: 40). Neutropenia was the most common G3/4 adverse event in Arm 2. 80% of pts (Arm 1: 16/20, Arm 2: 32/40; p = 0.87) met primary PSA endpoint {less than or equal to}4ng/mL at 28 weeks. PSA undetectable rate at 28 weeks was 50% and 43% in Arms 1 and 2 respectively (p = 0.5). Radiographic RR was 89% in both arms. 12 month biochemical PFS was 69% and 74% in Arms 1 and 2, respectively (p=0.72). TP53, PIK3 pathway mutations, 8q gains, and pretreatment CTCs were associated with reduced PSA PFS.

CONCLUSIONS: Palbociclib did not impact the outcome in RB intact mHSPC. Pretreatment CTC, TP53, and PIK3 pathway mutations, and 8q gain were associated with poor outcome.

Clinical Institute



Internal Medicine




Pathology & Laboratory Medicine