CARD: Randomized, open-label study of cabazitaxel (CBZ) vs abiraterone (ABI) or enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC)

Abstract

Background: Taxanes (docetaxel [DOC], CBZ) and androgen receptor-targeted therapies (ARTs; ABI, ENZ) are standard of care in mCRPC. The optimal treatment sequence is unknown. CARD (NCT02485691) compared CBZ vs ABI or ENZ in patients with mCRPC previously treated with DOC and the alternative ART. Method(s): Patients with mCRPC previously treated with >= 3 cycles of DOC and progressing = 75 yrs) were randomized. Median number of cycles was higher for CBZ vs ART (7 vs 4). rPFS was significantly improved with CBZ vs ART (median 8.0 vs 3.7 mo; HR 0.54; 95% CI 0.40-0.73; p < 0.0001). CBZ also robustly improved OS (median 13.6 vs 11.0 mo; HR 0.64; 95% CI 0.46-0.89; p = 0.0078) despite crossover, as well as PFS (median 4.4 vs 2.7 mo; p < 0.0001), confirmed PSA50 response (35.7% vs 13.5%; p = 0.0002) and tumor response (36.5% vs 11.5%; p = 0.004). Pain response and time to symptomatic skeletal events were also significantly improved with CBZ. Grade >= 3 adverse events (AEs) occurred in 56.3% vs 52.4% of patients with CBZ vs ART. For CBZ vs ART, main grade >= 3 AEs were: renal disorders (3.2% vs 8.1%); infections (7.9% vs 7.3%); musculoskeletal pain/discomfort (1.6% vs 5.6%); cardiac disorders (0.8% vs 4.8%); spinal cord/nerve root disorders (2.4% vs 4.0%); asthenia/fatigue (4.0% vs 2.4%); diarrhea, peripheral neuropathy and febrile neutropenia (3.2% vs 0% for each). AEs led to death in 7 vs 14 patients (5.6% vs 11.3%) for CBZ vs ART. Conclusion(s): CBZ significantly improved clinically important patient outcomes including rPFS and OS vs ART in patients with mCRPC previously treated with DOC and an alternative ART. CBZ should be the preferred option in this setting. Sanofi funded. Clinical trial identification: NCT02485691. Editorial acknowledgement: Editorial support was provided by Amber Wood, Danielle Lindley and Tina Wasmeier of MediTech Media and funded by Sanofi. Legal entity responsible for the study: Sanofi. Funding(s): Sanofi. Disclosure: R. de Wit: Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory Boards and speaker fees: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory Boards and speaker fees: Janssen; Advisory / Consultancy, Research grant / Funding (institution), Advisory Boards and institutional grants: Sanofi; Advisory / Consultancy, Research grant / Funding (self), Advisory Boards and institutional grants: Merck; Advisory / Consultancy, Research grant / Funding (institution), Advisory Boards and institutional grants: Bayer; Advisory / Consultancy, Research grant / Funding (self), Advisory Boards and institutional grants: Clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche. G. Kramer: Honoraria (self), Personal fess: Sanofi, Astellas, Takeda, Bayer, Janssen, Novartis, Ipsen, AstraZeneca; Research grant / Funding (self), Grant: Sanofi, Bayer. J. Eymard: Advisory / Consultancy, Board participation for Sanofi Aventis: Sanofi Aventis. J.S. de Bono: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Astellas Pharma; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Genentech/Roche; Honoraria (self), Advisory / Consultancy: Janssen Oncology; Honoraria (self), Advisory / Consultancy: Menarini Silicon Biosystems; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Sierra Oncology; Honoraria (self): Bioexcell; Advisory / Consultancy: Bayer; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy: Genmab; Advisory / Consultancy: GlaxoSmithKline; Advisory / Consultancy: Orion Pharma GmbH; Advisory / Consultancy: Eisai, BioXCel therapeutics. C.N. Sternberg: Honoraria (self): Janssen; Honoraria (self): AstraZeneca; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self): Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy: Pfizer; Honoraria (institution), Research grant / Funding (institution): Roche-Genentech, Bayer, Sanofi Genzyme, Janssen, Medivation, Exelixis. K. Fizazi: Honoraria (institution), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: Astellas; Honoraria (institution), Advisory / Consultancy: Astrazeneca; Honoraria (institution), Advisory / Consultancy: AAA; Honoraria (institution), Advisory / Consultancy: Bayer; Honoraria (institution), Advisory / Consultancy: Curevac; Honoraria (institution), Advisory / Consultancy: Essa; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: Orion; Honoraria (institution), Advisory / Consultancy: Sanofi. B. Tombal: Research grant / Funding (self): Astellas; Research grant / Funding (self): Janssen; Research grant / Funding (self), Non-remunerated activity/ies: Sanofi-Genzyme; Research grant / Funding (self): Amgen; Research grant / Funding (self): Ferring. A. Bamias: Honoraria (self): Astellas; Honoraria (self): Sanofi; Research grant / Funding (self): Janssen. J. Carles: Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson and Johnson; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas Pharma; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Speaker Bureau / Expert testimony: Asofarma. R. Iacovelli: Honoraria (self): Sanofi; Honoraria (self): Janssen; Honoraria (self): Pfizer; Honoraria (self): IPSEN; Honoraria (self): Novartis; Honoraria (self): BMS; Honoraria (self): MSD. B. Melichar: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Pfizer. A. Ozatilgan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Sanofi. C. Geffriaud-Ricouard: Full / Part-time employment: Sanofi. D. Castellano: Honoraria (self), Personal fees: Pfizer; Honoraria (self), Personal fees: Roche; Honoraria (self), Personal fees: Sanofi; Honoraria (self), Personal fees: Janssen; Honoraria (self), Personal fees: Astellas; Honoraria (self), Personal fees: Bayer; Honoraria (self), Personal fees: BMS; Honoraria (self), Personal fees: MSD; Honoraria (self), Personal fees: Merck Serono; Honoraria (self), Personal fees: Pierre Fabre; Honoraria (self), Personal fees: AstraZeneca; Honoraria (self), Personal fees: Lilly. All other authors have declared no conflicts of interest.Copyright © 2019 European Society for Medical Oncology