As reported at the European Society for Medical Oncology (ESMO) Congress 2019 (Abstract LBA13) and simultaneously published in The New England Journal of Medicine by Ronald de Wit, MD, and colleagues, the phase III CARD trial has shown improved imaging-based progression-free survival and overall survival with cabazitaxel vs an androgen signaling–targeted inhibitor (abiraterone or enzalutamide) among patients with metastatic castration-resistant prostate cancer who had disease progression on docetaxel and the alternative androgen signaling–targeted inhibitor.

Ronald de Wit, MD

Study Details

In the open-label trial, 255 patients were randomly assigned between November 2015 and November 2018 to receive cabazitaxel at 25 mg/m² every 3 weeks plus prednisone daily and granulocyte colony-stimulating factor (n = 129); or abiraterone at 1,000 mg/d plus prednisone or enzalutamide at 160 mg/d depending on previously received androgen signaling–targeted inhibitor treatment (n = 126; abiraterone = 59, enzalutamide = 67).

Eligible patients had disease progression during 12 months of treatment with abiraterone or enzalutamide before or after docetaxel treatment. The primary endpoint was imaging-based progression-free survival.

Imaging-Based Progression-Free Survival

Median follow-up was 9.2 months. Median imaging-based progression-free survival was 8.0 months in the cabazitaxel group vs 3.7 months with abiraterone or enzalutamide (hazard ratio [HR] = 0.54, P < .001). Hazard ratios for imaging-based progression-free survival were 0.57 (95% confidence interval [CI] = 0.36–0.90) for cabazitaxel vs enzalutamide and 0.44 (95% CI = 0.29–0.67) for cabazitaxel vs abiraterone.

Median overall survival was 13.6 months in the cabazitaxel group vs 11.0 months in the androgen signaling–targeted inhibitor group (HR = 0.64; P = .008). Median progression-free survival (including prostate-specific antigen, imaging-based, and pain progression) was 4.4 months vs 2.7 months (HR = 0.52; P < .001). Prostate-specific antigen response was observed in 35.7% vs 13.5% of patients (P < .001), and tumor response was observed in 36.5% vs 11.5% (P = .004).

Adverse Events

Adverse events of grade ≥ 3 occurred in 56.3% of patients receiving cabazitaxel and in 52.4% of those receiving an androgen signaling–targeted inhibitor. Adverse events more common with cabazitaxel treatment included asthenia or fatigue (4.0% vs 2.4%), diarrhea (3.2% vs 0%), peripheral neuropathy (3.2% vs 0%), and febrile neutropenia (3.2% vs 0%); those more common with abiraterone or enzalutamide were renal disorders (8.1% vs 3.2%), musculoskeletal pain or discomfort (5.6% vs 1.6%), cardiac disorders (4.8% vs 0.8%), and spinal cord or nerve-root disorders (4.0% vs 2.4%). Neutropenia of grade ≥ 3 occurred in 44.7% of the cabazitaxel group.

Serious adverse events occurred in 38.9% vs 38.7% of patients. Adverse events led to treatment discontinuation in 19.8% vs 8.9%. Adverse events led to death between randomization and 30 days after last treatment administration in 5.6% vs 11.3% of patients.

The investigators concluded, “Cabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen signaling–targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who had been previously treated with docetaxel and the alternative androgen signaling–targeted agent (abiraterone or enzalutamide).”

Disclosure: The study was funded by Sanofi. For full disclosures of the study authors, visit nejm.org.