A randomized phase II study of cabazitaxel (CAB) vs (ABI) abiraterone or (ENZ) enzalutamide in poor prognosis metastatic castrationresistant prostate cancer (mCRPC).

Abstract

Background: The optimal treatment for poor prognosis mCRPC is undefined and includes either taxane chemotherapy or androgen receptor (AR) targeted therapy, emphasizing the need for predictive biomarkers. Method(s): Patients (pts) with poor prognosis (liver metastases, early CRPC (<12 months from ADT start), and/or>3 of 6 poor prognostic criteria (Chi et al, Annals of Oncol, 2016)) were randomized to receive CAB (Arm A) or AR targeted therapy (Arm B, ABI or ENZ by investigator choice) with cross over at progression. No prior ABI or ENZ was permitted, but prior docetaxel allowed. Primary objective was to determine the clinical benefit rate (CBR) (PSA decline >= 50% (PSA50), objective response (OR), or stable disease (SD) >= 12 weeks). Other endpoints included time to PSA progression (TTPP), time to progression (TTP), and overall survival (OS). Serial plasma was sampled for circulating tumour DNA (ctDNA). Result(s): 95 pts were randomized (Arm A: 45, Arm B: 50). Poor prognosis was based on liver mets in 18%, early CRPC in 88%, and 30% by prognostic criteria. Other baseline factors: median age 68 years, elevated LDH in 41%, elevated ALK PHOS in 52%, ECOG PS 0-1 in 94%, 52% had prior docetaxel (half for castration sensitive disease). Median duration of therapy was 5.8 months (m) for Arm A and 4.5mfor Arm B. Treatment discontinuation reasons included disease progression (A vs B: 40% vs 46%) and toxicity (11% vs 4%). Outcomes are summarized in table. In 58 pts with available results, baseline ctDNA fraction>2% correlated with TTP (median 3.4mvs 10.8 m, p=0.011) and OS (median 15.5mvs not reached (NR), p=0.002). Genomic alterations in AR, RB1, TP53, PI3K pathway, and DNA repair were present in 69%, 36%, 51%, 40%, and 15%. (Table Presented) Conclusion(s): Treatment with CAB vs ABI/ENZA resulted in similar outcomes. There was a trend in favour of CAB for survival. Genomic correlations will be presented.