CARD

By 2019 most men with castration-resistant prostate cancer were being offered abiraterone or enzalutamide, and when one failed, the other. CARD tested whether that switch is as good as chemotherapy.

It randomised 255 men who had received docetaxel and progressed within 12 months on abiraterone or enzalutamide to cabazitaxel 25 mg/m2 every 3 weeks with prednisone and granulocyte colony-stimulating factor, or to the other androgen receptor pathway inhibitor.

At a median 9.2 months, imaging-based progression or death had occurred in 95 of 129 men (73.6 percent) on cabazitaxel against 101 of 126 (80.2 percent) on the second inhibitor, hazard ratio 0.54 (95 percent confidence interval 0.40 to 0.73, p<0.001). Median imaging-based progression-free survival was 8.0 against 3.7 months. Median overall survival was 13.6 against 11.0 months, hazard ratio 0.64 (0.46 to 0.89, p=0.008). Progression-free survival was 4.4 against 2.7 months (0.52, 0.40 to 0.68, p<0.001), PSA response occurred in 35.7 against 13.5 percent (p<0.001) and tumour response in 36.5 against 11.5 percent (p=0.004).

Adverse events of grade 3 or higher occurred in 56.3 percent on cabazitaxel and 52.4 percent on the second inhibitor, so the chemotherapy was not meaningfully more toxic in this population. CARD is the clearest evidence in prostate cancer that switching within a drug class after early failure is a waste of time.