3965 - CARD: Randomized, open-label study of cabazitaxel (CBZ) vs abiraterone (ABI) or enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC)

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.

Methods

Patients with mCRPC previously treated with ≥ 3 cycles of DOC and progressing ≤ 12 months (mo) on an alternative ART, in any order, were randomized 1:1 to CBZ (25 mg/m² IV Q3W + prednisone + G-CSF) vs ABI (1000 mg PO + prednisone) or ENZ (160 mg PO). Randomization was stratified by ECOG PS (0/1 vs 2), time to progression on prior ART (≤ 6 vs 6–12 mo) and ART timing (before vs after DOC). Primary endpoint was radiographic PFS (rPFS), with 196 rPFS events needed to test HR 0.67 for CBZ (80% power, 2-sided alpha 0.05). Secondary efficacy endpoints and safety were assessed.

Results

Overall, 255 patients (median age 70, 31.0% ≥ 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.

Conclusions

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

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.