Molecular and immune profiles linked to androgen response categories in metastatic castration-resistant prostate cancers (mCRPC)

Prostate cancer is a heterogenous disease and can be broadly categorized into androgen responsive and androgen indifferent groups. Robust biomarkers to identify them and enable the development of therapeutic strategies specific to each, remain to be defined. We conducted a dynamic, modular clinical trial ("DynAMo") in which 192 men with mCRPC were segregated based on Satisfactory (≥ 50% PSA decline from baseline and <5 CTC/7.5mL) versus Unsatisfactory marker status after 8-weeks of abiraterone, prednisone and apalutamide (ApA). Those with Satisfactory status (n=128, 67%) were randomized to continue ApA alone (Module 2A) or with ipilimumab (Module 2B). Median overall survival (OS) and 95% CI was 46.4 (39.2, 68.2) months and 41.4 (33.3, 49.9) months respectively. Patients with Unsatisfactory marker status (n=64, 33%) had carboplatin+cabazitaxel chemotherapy added to ApA (Module 3) and had an OS and 95% CI of 18.7 (14.3, 26.3) months. As part of this study, poly(A) RNA was extracted from 140 fresh frozen cores obtained from 136 patients during pre-treatment biopsies of metastatic sites. Of these, 21 (15.0%) yielded insufficient or poor-quality RNA. Of the 119 cores that were subject to bulk RNA sequencing, 56 (47.1%) from 56 patients passed quality control filters (i.e., RNA total reads ≥60 million, exonic rates ≥0.7, and ≥20,000 genes detected). The sequencing results from these 56 patient samples are provided here.