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The authors of this multicenter, phase II trial randomized 95 men with metastatic castration-resistant prostate cancer (mCRPC) to cabazitaxel plus prednisone or physician’s choice of androgen receptor pathway inhibitor (enzalutamide or abiraterone plus prednisone). All patients were androgen receptor pathway inhibitor–naïve and had poor prognostic features. The clinical benefit rate was higher with cabazitaxel treatment (80% vs 62%). Overall survival was numerically longer (median 37 vs 15.5 months) but did not reach statistical significance.
These findings provide supporting evidence for the general clinical perspective that patients with poor prognosis mCRPC may be better treated with upfront chemotherapy. Baseline and on-treatment change in ctDNA demonstrated prognostic value.
– Paul J. Hampel, MD
Abstract
This abstract is available on the publisher's site.
PURPOSE
Treatment for poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting.
PATIENTS AND METHODS
This multicentre, randomised, open-label, phase 2 trial recruited patients with ARPI-naïve mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1:1 to receive cabazitaxel plus prednisone (Group A) or physician's choice of enzalutamide or abiraterone plus prednisone (Group B) at standard doses. Patients could cross-over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as PSA response ≥50%, radiographic response, or stable disease ≥12 weeks).
RESULTS
95 patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in Group A versus B (80% vs 62%, p=0.039). Overall survival was not different between Group A and B (median 37.0 vs 15.5 months, HR=0.58, p=0.073) nor was time to progression (median 5.3 vs 2.8 months, HR=0.87, p=0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32% vs ARPI 0%), diarrhea (9% vs 0%), infection (9% vs 0%) and fatigue (7% vs 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, p < 0.001; HR = 4.03, p < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, p < 0.001).
CONCLUSIONS
Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naïve poor prognosis mCRPC. CtDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.
Citation: Annals of Oncology
Cabazitaxel Versus Abiraterone or Enzalutamide in Poor Prognosis Metastatic Castration-Resistant Prostate Cancer: A Multicentre, Randomised, Open-Label, Phase 2 Trial
Ann. Oncol 2021 Apr 06;[EPub Ahead of Print], M Annala, S Fu, JVW Bacon, J Sipola, N Iqbal, C Ferrario, M Ong, D Wadhwa, SJ Hotte, G Lo, B Tran, LA Wood, JR Gingerich, SA North, CJ Pezaro, JD Ruether, SS Sridhar, HML Kallio, DJ Khalaf, A Wong, K Beja, E Schönlau, S Taavitsainen, M Nykter, G Vandekerkhove, AA Azad, AW Wyatt, KN Chi
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.