On September 14, 2017, the microtubule inhibitor cabazitaxel (Jevtana) was approved at the lower dose of 20 mg/m2 every 3 weeks in combination with prednisone for treatment of patients with metastatic castration-resistant prostate cancer previously treated with a docetaxel-containing regimen.1,2 Cabazitaxel was approved in this indication at a dose of 25 mg/m2 every 3 weeks in 2010. A dose of 25 mg/m2 can still be used in select patients at the discretion of the treating physician.
Supporting Efficacy Data
Approval was based on data from the noninferiority multicenter open-label phase III PROSELICA trial, in which 1,200 patients received cabazitaxel at 25 mg/m2 (n = 602) or 20 mg/m2 (n = 598).2,3 The trial was conducted as a postmarketing requirement to evaluate a lower dose compared with the approved dose of 25 mg/m2.
For management of adverse events, patients receiving a dose of 20 mg/m2 may have the dose reduced to 15 mg/m2; those starting at 25 mg/m2 may have the dose reduced to 20 mg/m2, with further reduction to 15 mg/m2 being considered.
The trial demonstrated noninferiority in overall survival with cabazitaxel at 20 mg/m2. In the intent-to-treat population, median overall survival was 13.4 months in the lower-dose group vs 14.5 months in the higher-dose group (hazard ratio [HR] = 1.024, 97.78% confidence interval [CI] = 0.886–1.184; noninferiority margin = 1.214). In the per-protocol population, median overall survival was 15.1 vs 15.9 months (HR = 1.042, 97.78% CI = 0.886–1.224).
Supporting Safety Data
In the phase III trial, any grade adverse events that were ≥ 5% more common in the 25 mg/m2 vs 20 mg/m2 groups were diarrhea (40% vs 31%), nausea (32% vs 25%), hematuria (21% vs 14%), asthenia (20% vs 15%), decreased appetite (19% vs 13%), neutropenia (11% vs 3%), and febrile neutropenia (9% vs 2%). Grade 3 or 4 adverse events occurring ≥ 5% more frequently in the higher-dose group were neutropenia (10% vs 2%) and febrile neutropenia (9% vs 2%). Grade 3 or 4 laboratory abnormalities were more common in the higher-dose group, including neutropenia in 73% vs 42%, leukopenia in 60% vs 29%, anemia in 14% vs 10%, and thrombocytopenia in 4% vs 3%.
Adverse events led to treatment discontinuation in 20% vs 17% of patients, with the most common causes being fatigue and hematuria. In the higher-dose group, the cabazitaxel dose was reduced to 20 mg/m2 in 128 patients (22%), from 20 to 15 mg/m2 in 19 (3%), and from 15 to 12 mg/m2 in 1. In the 20 mg/m2 group, 58 patients (10%) had the dose reduced to 15 mg/m2, and 9 patients (2%) had the dose reduced from 15 to 12 mg/m2.
Death within 30 days of the last study drug dose (5.4% vs 3.8%) and early infection-related death within 30 days of treatment initiation (1.3% vs 0.7%) were more common in the 25 mg/m2 group. All of the early infection-related deaths occurred in patients aged > 60 years. Other fatal adverse events included cerebral hemorrhage, respiratory failure, paralytic ileus, diarrhea, acute pulmonary edema, disseminated intravascular coagulation, renal failure, sudden death, cardiac arrest, ischemic stroke, diverticular perforation, and cardiorenal syndrome.
The recommended dose of cabazitaxel is now 20 mg/m2 given every 3 weeks via 1-hour intravenous infusion in combination with daily oral prednisone at 10 mg. A dose of 25 mg/m2 can be used in select patients at the discretion of the treating health-care provider.
For management of adverse events, patients receiving a dose of 20 mg/m2 may have the dose reduced to 15 mg/m2. Patients starting at 25 mg/m2 may have the dose reduced to 20 mg/m2, with additional reduction to 15 mg/m2 being considered. ■
1. U.S. Food and Drug Administration: FDA approves lower dose of cabazitaxel for prostate cancer. Available at www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm576147.htm. Accessed November 21, 2017.
2. Jevtana (cabazitaxel) injection prescribing information, Sanofi-Aventis, September 2017. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2017/201023s019lbl.pdf. Accessed November 21, 2017.
3. Eisenberger M, Hardy-Bessard AC, Kim CS, et al: Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in post-docetaxel patients with metastatic castration-resistant prostate cancer-PROSELICA. J Clin Oncol 35:3198-3206, 2017.
Health-care professionals should report all serious adverse events suspected to be associated with the use of any medicine or device to FDA’s MedWatch Reporting System by completing a form online at www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178), by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).