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.
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).
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).
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.
Annals of oncology : official journal of the European Society for Medical Oncology. 2021 Apr 06 [Epub ahead of print]
M Annala, S Fu, J V W Bacon, J Sipola, N Iqbal, C Ferrario, M Ong, D Wadhwa, S J Hotte, G Lo, B Tran, L A Wood, J R Gingerich, S A North, C J Pezaro, J D Ruether, S S Sridhar, H M L Kallio, D J Khalaf, A Wong, K Beja, E Schönlau, S Taavitsainen, M Nykter, G Vandekerkhove, A A Azad, A W Wyatt, K N Chi
Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada; Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, Tampere, Finland., Department of Medical Oncology, BC Cancer, Vancouver, British Columbia, Canada; Oncology, School of Medical Sciences, University of Auckland, Auckland, New Zealand., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, Tampere, Finland., Medical Oncology, Saskatoon Cancer Centre, University of Saskatchewan, Saskatoon, Canada., Jewish General Hospital, McGill University, Montréal, Quebec, Canada., Department of Medicine, Division of Medical Oncology, The Ottawa Hospital and the University of Ottawa, Ottawa, Ontario, Canada., BC Cancer - Kelowna Centre, Kelowna, British Columbia, Canada., Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada., Department of Medical Oncology, R. S. McLaughlin Durham Regional Cancer Centre, Lakeridge Health, Oshawa, Canada., Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., QEII Health Sciences Centre, Halifax, Canada., Department of Medical Oncology and Hematology, CancerCare Manitoba, Winnipeg, Canada., Department of Oncology, University of Alberta, Edmonton, Alberta, Canada., Eastern Health Clinical School, Monash University, Victoria, Australia; Department of Oncology, Eastern Health, Victoria, Australia., Tom Baker Cancer Centre, Calgary, Alberta, Canada., Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada., Department of Medical Oncology, BC Cancer, Vancouver, British Columbia, Canada., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada. Electronic address: ., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada; Department of Medical Oncology, BC Cancer, Vancouver, British Columbia, Canada. Electronic address: .