September 14, 2017
On September 14, 2017, the U.S. Food and Drug Administration approved a lower dose of cabazitaxel (20 mg/m2 every 3 weeks) (JEVTANA®, Sanofi-Aventis) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing treatment regimen. Cabazitaxel (25 mg/m2 every 3 weeks) was approved for this indication in 2010.
The approval was based on data from a noninferiority, multicenter, randomized, open-label trial (PROSELICA) of 1200 patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing regimen. This trial was conducted as a post-marketing requirement to evaluate a lower dose compared with the approved dose of 25 mg/m2. Patients received either cabazitaxel 25 mg/m2 (n=602) or the 20 mg/m2 (n=598) dose.
The trial demonstrated noninferiority in overall survival (OS) of cabazitaxel 20 mg/m2 in comparison with 25 mg/m2 in an intent-to-treat population. The estimated median OS was 13.4 months for patients on the lower dose compared with 14.5 months for patients receiving the higher dose (hazard ratio=1.024; 97.78% CI: 0.886, 1.184). Based on the per-protocol population, the estimated median OS was 15.1 and 15.9 months on cabazitaxel 20 mg/m2 and cabazitaxel 25 mg/m2, respectively (hazard ratio=1.042; 97.78% CI: 0.886, 1.224).
The major safety findings, myelosuppression, infections and increased toxicity, occurred with greater frequency on the 25 mg/m2 arm compared to the lower dose. Deaths within 30 days of the last study drug dose (5.4% vs. 3.8%), and early infection-related deaths within 30 days of the treatment initiation (1.3% vs 0.7%) were more common on the 25 mg/m2 arm compared to the 20 mg/m2 arm. All of the early infection-related deaths occurred in patients greater than 60 years of age. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.
Adverse reactions and laboratory abnormalities occurring in greater than 10% of patients treated with cabazitaxel on clinical trials were neutropenia, anemia, leukopenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, and anorexia. Grade 3-4 infections were reported in 20% patients on the 25 mg/m2 arm and 10% patients on the lower dose. Febrile neutropenia occurred in 9% of patients on the 25 mg/m2 arm and in 2% on the 20 mg/m2 arm. The most common reasons for dose discontinuation were fatigue and hematuria.
The recommended dose of cabazitaxel is 20 mg/m2 administered every three weeks as a one-hour intravenous infusion in combination with oral prednisone 10 mg administered daily. A dose of 25 mg/m2 can be used in select patients at the discretion of the treating healthcare provider.
The full prescribing information is available at:
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).