Two different doses of cabazitaxel failed to show superiority with regard to overall survival (OS) over docetaxel as first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), according to results of a phase III randomized trial.
“Recent years have seen the emergence of new therapeutic approaches for mCRPC,” wrote study authors led by Stéphane Oudard, MD, PhD, of René Descartes University in Paris. Cabazitaxel, a second-generation taxane, has demonstrated an OS benefit compared with mitoxantrone in mCRPC patients previously treated with docetaxel, and is approved as a second-line option. Other preclinical and clinical data, however, support the possibility that the agent might be effective in the frontline setting.
The FIRSTANA trial was a phase III study including 1,168 treatment-naive mCRPC patients, randomized to one of three groups: cabazitaxel 20 mg/m2 (C20; 389 patients); cabazitaxel 25 mg/m2 (C25; 388 patients); or docetaxel 75 mg/m2 (D75; 391 patients). Results of the study were published online ahead of print in the Journal of Clinical Oncology.
The median OS was 24.5 months in the C20 group, 25.2 months in the C25 group, and 24.3 months in the D75 group. The hazard ratio (HR) for OS for the C20 patients compared with D75 patients was 1.01 (95% CI, 0.85–1.20; P = .997); for the C25 patients vs the D75 group, the HR was 0.98 (95% CI, 0.82–1.16; P = .757).
There were also no differences between the two cabazitaxel groups and the docetaxel groups with regard to tumor progression-free survival (PFS), prostate-specific antigen PFS, pain PFS, and a composite measure of PFS.
The overall response rate was 32.4% with C20, 41.6% with C25, and 30.9% with D75. The C20 group’s overall response rate was significantly better than the D75 group’s rate (P = .037). The three groups “demonstrated equivalent impact” on health-related quality-of-life measures, with the exception of physical well-being, which showed a longer median time to deterioration in the C20 group than in the D75 group.
The treatments showed differing patterns of toxicity. The rates of treatment-emergent grade 3/4 adverse events were 41.2% with C20, 60.1% with C25, and 46% with D75. Cabazitaxel patients had more frequent febrile neutropenia, neutropenic infection, diarrhea, and hematuria, while docetaxel patients were more likely to experience peripheral neuropathy, stomatitis, peripheral edema, alopecia, and nail disorders.
“The lack of difference between cabazitaxel and docetaxel with respect to OS and other endpoints suggests that these two agents are not distinct in efficacy when administered as first-line therapy to patients with mCRPC,” the authors wrote. “The different safety profiles of the two taxane chemotherapies, along with similar efficacy, may offer additional flexibility to prescribing physicians.”