Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial

Annala, M; Fu, S; Bacon, JVW; Sipola, J; Iqbal, N; Ferrario, C; Ong, M; Wadhwa, D; Hotte, SJ; Lo, G; Tran, B; Wood, LA; Gingerich, JR; North, SA; Pezaro, CJ; Ruether, JD; Sridhar, SS; Kallio, HML; Khalaf, DJ; Wong, A; Beja, K; Schonlau, E; Taavitsainen, S; Nykter, M; Vandekerkhove, G; Azad, AA; Wyatt, AW; Chi, KN

Author(s): Annala, M; Fu, S; Bacon, JVW; Sipola, J; Iqbal, N; Ferrario, C; Ong, M; Wadhwa, D; Hotte, SJ; Lo, G; Tran, B; Wood, LA; Gingerich, JR; North, SA; Pezaro, CJ; Ruether, JD; Sridhar, SS; Kallio, HML; Khalaf, DJ; Wong, A; Beja, K; Schonlau, E; Taavitsainen, S; Nykter, M; Vandekerkhove, G; Azad, AA; Wyatt, AW; Chi, KN;
Details: Publication Year 2021-07,Volume 32,Issue #7,Page 896-905
Journal Title: Annals of Oncology
Publication Type: Research article
Abstract: BACKGROUND: Treatment of 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 II trial recruited patients with ARPI-naive 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 prostate-specific antigen response >/=50%, radiographic response, or stable disease >/=12 weeks). RESULTS: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80% versus 62%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) = 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR = 0.87, P = 0.52). The most common first-line treatment-related grade >/=3 adverse events were neutropenia (cabazitaxel 32% versus ARPI 0%), diarrhoea (9% versus 0%), infection (9% versus 0%), and fatigue (7% versus 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-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.
Keywords: Androgen Antagonists/therapeutic use; Androstenes; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Benzamides; Humans; Male; Nitriles; Phenylthiohydantoin; Prednisone/adverse effects; Prognosis; *Prostatic Neoplasms, Castration-Resistant/drug therapy; Taxoids/therapeutic use; Treatment Outcome; androgen receptor pathway inhibitor; circulating tumor DNA (ctDNA); plasma cell-free DNA; prostate cancer; taxane chemotherapy
Department(s): Medical Oncology
PubMed ID: 33836265
Publisher's Version: https://doi.org/10.1016/j.annonc.2021.03.205
Open Access at Publisher's Site: https://doi.org/10.1016/j.annonc.2021.03.205
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-05-23 08:13:50

Last Modified: 2025-05-23 08:15:07