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

Document Type

Article

Publication Date

3-16-2021

Publication Title

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

Keywords

california; jwci

Abstract

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

Cancer

Department

Internal Medicine

Department

Oncology

Department

Pathology & Laboratory Medicine

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