In June 2010, the FDA approved cabazitaxel, a semi-synthetic taxane derivative, for men with metastatic CRPC previously treated with a docetaxel-containing regimen. An international randomized phase 3 trial (TROPIC) randomized 755 men with progressive metastatic CRPC to receive cabazitaxel 25 mg/m2 or mitoxantrone 12 mg/m2, each with daily prednisone.416 A 2.4 month improvement in overall survival was demonstrated with cabazitaxel compared to mitoxantrone (HR, 0.72; P < .0001). The improvement in survival was balanced against a higher toxic death rate with cabazitaxel (4.9% vs. 1.9%), which was due, in large part, to differences in rates of sepsis and renal failure. Febrile neutropenia was observed in 7.5% of cabazitaxel-treated men vs. 1.3% of mitoxantrone-treated men. The incidences of severe diarrhea (6%), fatigue (5%), nausea/vomiting (2%), anemia (11%), and thrombocytopenia (4%) also were higher in cabazitaxel-treated men, which indicated the need for vigilance and treatment or prophylaxis in this setting to prevent febrile neutropenia. The survival benefit was sustained at an updated analysis with median follow-up 25.5 months.417
The phase 3 open-label, multinational, non-inferiority PROSELICA study compared 20 mg/m2 cabazitaxel with 25 mg/m2 cabazitaxel in 1200 patients with mCRPC who progressed on docetaxel.418 The lower dose was found to be noninferior to the higher dose for median OS (13.4 mo [95% CI, 12.19–14.88] vs 14.5 mo [95% CI, 13.47–15.28]), and grade 3/4 adverse events were decreased (39.7% vs 54.5%). In particular, grade 4 neutropenia rates were 21.3% and 48.6% for the lower and higher dose groups, respectively. Cabazitaxel at 25 mg/m2 every 3 weeks, with or without growth factor support remains standard of care for fit patients. However, in frail patients, cabazitaxel at 20 mg/m2 every 3 weeks, with or without growth factor support, can be considered.
Recent results from the phase 3 FIRSTANA study suggested that cabazitaxel has clinical activity in patients with chemotherapy-naïve mCRPC.419 Median OS, the primary endpoint, was similar between 20 mg/m2 cabazitaxel, 25 mg/m2 cabazitaxel, and 75 mg/m2 docetaxel (24.5 mo, 25.2 mo, and 24.3 mo, respectively). Cabazitaxel was associated with lower rates of peripheral neuropathy than docetaxel, particularly at 20 mg/m2 (12% vs 25%). Therefore, patients who are not candidates for docetaxel, who are intolerant of docetaxel, or who have pre-existing mild peripheral neuropathy should be considered for cabazitaxel.