Reduced-Dose Cabazitaxel After Docetaxel in Metastatic Castration-Resistant Prostate Cancer
In the phase III PROSELICA trial reported by Eisenberger et al in the Journal of Clinical Oncology, a cabazitaxel (Jevtana) dose of 20 mg/m2 (C20) was noninferior for overall survival vs the currently recommended dose of 25 mg/m2 (C25) after docetaxel treatment in metastatic castration-resistant prostate cancer. Both doses had been recommended for phase II and III testing, and there was evidence that the lower dose was associated with reduced toxicity.
Study Details
In the open-label trial, 1,200 patents from 172 sites in 22 countries were randomized between April 2011 and December 2013 to receive C20 (n = 598) or C25 (n = 602) plus prednisone at 10 mg. Noninferiority of C20 was to be established if the upper boundary of the 98.89% confidence interval [CI] of the hazard ratio (HR) for overall survival vs C25 did not exceed 1.214.
Overall Survival
Median overall survival was 13.4 months in the C20 group vs 14.5 months in the C25 group (HR = 1.024; the upper boundary of the HR CI was 1.184, meeting the noninferiority margin). Median progression-free survival was 2.9 months vs 3.5 months (HR = 1.099, 95% CI = 0.974–1.240). The C25 group exhibited better outcomes in prostate-specific antigen (PSA) response (29.5% vs 42.9%, P < .001) and time to PSA progression (median 5.7 vs 6.8 months, HR = 1.195, 95% CI = 1.025–1.393).
Adverse Events
The most common adverse events of any grade were diarrhea (30.7% in the C20 group vs 39.8% in the C25 group), fatigue (24.7% vs 27.1%), and hematuria (14.1% vs 20.8%). Grade ≥ 3 adverse events occurred in 39.7% vs 54.5%, with the most common being fatigue (2.6%) and febrile neutropenia (2.1%) in the C20 group and febrile neutropenia (9.2%) and hematuria (4.2%) in the C25 group. Grade ≥ 3 hematologic abnormalities included neutropenia in 41.8% vs 73.3% and leukopenia in 28.9% vs 59.5%. Serious adverse events occurred in 30.5% vs 43.2% of patients, and adverse events possibly related to treatment resulted in treatment discontinuation in 16.4% vs 19.5%. Health-related quality of life did not differ between the groups.
The investigators concluded: “The efficacy of cabazitaxel in postdocetaxel patients with [metastatic castration-resistant prostate cancer] was confirmed. The noninferiority end point was met…. Secondary efficacy end points favored C25. Fewer adverse events were observed with C20.”
The study was supported by Sanofi.
Mario Eisenberger, MD, of The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, is the corresponding author of the Journal of Clinical Oncology article.
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