Drug Sequencing in Metastatic Castration-Resistant Prostate Cancer

In patients with metastatic castration-resistant prostate cancer (mCRPC), the optimal sequence of administering approved therapeutic agents remains undefined. Complicating this fact has been the movement of many agents (e.g., abiraterone, docetaxel, enzalutamide, apalutamide, and darolutamide) to a point earlier in the disease course, as well as cross-resistance between agents.

Now, investigators have conducted an industry-sponsored, multicenter, open-label, randomized study (CARD) to determine whether the next-generation taxane cabazitaxel would be more effective than an androgen-signaling–targeted inhibitor (ASTI; abiraterone or enzalutamide) in men with mCRPC who had disease progression within 12 months of receiving the alternative ASTI. Among 255 patients (median age, 70 years), about 95% had performance status 1, and 44% had a duration of response to first androgen-deprivation therapy of <1 year.

At a median follow-up of 9.2 months, median progression-free survival (the primary endpoint) was longer with cabazitaxel than with abiraterone or enzalutamide (8.0 vs. 3.7 months; hazard ratio, 0.54; P<0.001), as was median overall survival (13.6 vs. 11.0 months; HR, 0.64; P=0.008). A similar number of grade 3 or greater adverse events occurred in the cabazitaxel and abiraterone/enzalutamide groups (56% and 52%, respectively).