First-Line Cabazitaxel vs Docetaxel in Metastatic Castration-Resistant Prostate Cancer

Key Points

  • In the first-line treatment of metastatic castration-resistant prostate cancer, there was no difference in overall survival observed for cabazitaxel vs docetaxel regimens.
  • However, toxicity profiles differed, with lower-dose cabazitaxel being associated with less toxicity overall.

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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