Overall survival from PANTHER: A multicenter trial of apalutamide, abiraterone acetate plus prednisone in Black and White patients with metastatic castration-resistant prostate cancer (mCRPC).

Background: ACIS was an international phase III trial comparing apalutamide (A) plus abiraterone acetate and prednisone (AAP) to AAP in patients (pts) with mCRPC. Recognizing that lack of diversity in clinical trials is a major challenge to real-world translation of outcomes, we purposely designed to PANTHER to oversample Black pts compared to our catchment area demographics to estimate clinical outcomes among Black and White pts with mCRPC, accrued in parallel, single arm cohorts and treated with A+AAP. Here we report the long term radiographic progression-free survival (rPFS) and overall survival (OS) for both cohorts. Methods: This parallel cohort multicenter study treated androgen receptor pathway inhibitor naïve mCRPC pts with oral apalutamide (240 mg/d), abiraterone (1000 mg/d) and prednisone (10 mg/d) (AAAP) continuously until disease progression, unacceptable toxicity or 2 years, at which point patients were switched to standard of care. The primary endpoint is rPFS; secondary endpoints were to estimate (OS) and best PSA response among Black and White pts, separately. The target number of rPFS events was 26 per group. Exploratory endpoints included safety and correlative biomarkers of outcome by race and ancestry. Results: Between July 2017 and January 2021, we enrolled 43 Black and 50 White pts from 8 sites. Key baseline prognostic factors for the Black and White cohorts, respectively included: Gleason score 8-10 (56%; 56%), KPS 70-80% (26%; 18%), median age (67; 72), median PSA 15.20; 17.56), median time from diagnosis to enrollment (4.6 years; 3.3 years), visceral metastases (23.7%; 18.0%), prior docetaxel (33%; 44%). At the time of the abstract submission, there were 22 and 40 rPFS events, and 20 and 35 deaths in Black patients and White pts, respectively. Median follow up was 56 months (95% CI 50, 62) and 62 months (95% CI 56, NR) for Black and White pts, respectively. 24 months rPFS rate was 61% (95% CI 49, 78) and 38% (95% CI 27, 54) for Black and White pts, respectively. 36 months OS rate was 68% (95% CI 55, 83) and 50% (95% CI 37, 66) for Black and White pts, despite discontinuing study medications at 2 years and switching to standard of care. Conclusions: We hypothesize that treatment with the combination of A+AAP may result in clinical efficacy in Black men with mCRPC. Further prospectively powered studies of dual androgen receptor pathway inhibition with AAP among Black men with advanced prostate cancer are needed to determine the potential clinical benefits in this understudied population.

Duke Scholars

Author Linda Marie Sutton Medicine, Medical Oncology

Author Michael Roger Harrison Medicine, Medical Oncology

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics

Author Jennifer Freedman Medicine, Medical Oncology

Author Lauren Howard  

Author Steven Patierno Medicine, Medical Oncology

Author Andrew John Armstrong Medicine, Medical Oncology

Author Daniel James George Medicine, Medical Oncology