First-Line Cabazitaxel vs Docetaxel in Metastatic Castration-Resistant Prostate Cancer
The phase III FIRSTANA trial has shown no difference in overall survival with two dose regimens of cabazitaxel (Jevtana) vs docetaxel in the first-line treatment of metastatic castration-resistant prostate cancer. Results were reported by Oudard et al in the Journal of Clinical Oncology. Cabazitaxel is currently approved with prednisone for treatment of hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.
Study Details
In the open-label trial, 1,168 men from 159 sites in 25 countries were randomized between May 2011 and October 2013 to receive cabazitaxel at 20 mg/m2 (n = 389), cabazitaxel at 25 mg/m2 (n = 388), or docetaxel at 75 mg/m2 intravenously (n =3 91) once every 3 weeks plus oral prednisone at 10 mg daily. The primary endpoint was overall survival.
Overall Survival
Median overall survival was 24.5 months in the cabazitaxel 20 mg/m2 group (hazard ratio [HR] vs docetaxel = 1.01, P = .997), 25.2 months in the cabazitaxel 25 mg/m2 group (HR vs docetaxel = 0.97, P = .757), and 24.3 months in the docetaxel group. Composite median progression-free survival was 4.4 months (HR = 1.06, P = .422), 5.1 months (HR = 0.99, P = .804), and 5.3 months, respectively.
The radiographic tumor response rate (32.4% in cabazitaxel 20 mg/m2 group) was higher in the cabazitaxel 25 mg/m2 group vs the docetaxel group (41.6% vs 30.9%, nominal P = .037, without multiplicity test adjustment). No significant differences among the groups were observed for tumor or prostate-specific antigen progression-free survival; pain progression-free survival was better in the docetaxel group than in the cabazitaxel 25 mg/m2 group (HR = 1.19, P = .035).
Toxicity
Grade 3 or 4 treatment-related adverse events occurred in 41.2%, 60.1%, and 46.0% in the 3 groups, respectively. Any-grade treatment-related febrile neutropenia (12% [2% with lower-dose cabazitaxel] vs 8%), diarrhea (50% [33%] vs 37%), and hematuria (25% [20%] vs 4%) were more common with cabazitaxel at 25 mg/m2, whereas peripheral neuropathy (25% vs 12% [12%]), peripheral edema (20% vs 8% [10%]), alopecia (39% vs 13% [9%]), and nail disorders (9% vs 1% [< 1%]) were more common with docetaxel. Treatment was discontinued due to adverse events in 25.2%, 31.7%, and 33.9% of patients, respectively.
The investigators concluded: “[Cabazitaxel at 20 mg/m2 and cabazitaxel at 25 mg/m2] did not demonstrate superiority for [overall survival] versus [docetaxel at 75 mg/m2] in patients with chemotherapy-naive [metastatic castration-resistant prostate cancer]. Tumor response was numerically higher with [cabazitaxel at 25 mg/m2] versus [docetaxel]; pain [progression-free survival] was numerically improved with [docetaxel] versus [cabazitaxel at 25 mg/m2]. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with [cabazitaxel at 20 mg/m2].”
The study was supported by Sanofi.
Stéphane Oudard, MD, PhD, of René Descartes University, is the corresponding author of the Journal of Clinical Oncology article.
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