No Survival Benefit for Cabozantinib Reported in Previously Treated Metastatic Castration-Resistant Prostate Cancer
Smith et al found no improvement in overall survival with cabozantinib (Cometriq) vs prednisone in patients with previously treated metastatic castration-resistant prostate cancer, in the phase III COMET-1 trial reported in the Journal of Clinical Oncology. Cabozantinib, which inhibits MET, VEGF (vascular endothelial growth factor) receptor 2, and other tyrosine kinases, was associated with benefit in some secondary outcome measures.
Study Details
In the double-blind trial, 1,028 patients with progressive disease after docetaxel and abiraterone (Zytiga) or enzalutamide (Xtandi) from 216 sites in 14 countries in Europe (76% of patients), North America (15%), and Australia (6%) were randomized 2:1 between July 2012 and November 2014 to receive cabozantinib at 60 mg once daily (n = 682) or prednisone at 5 mg twice daily (n = 346). Randomization was stratified by prior cabazitaxel, baseline pain severity, and Eastern Cooperative Oncology Group performance status. The primary endpoint was overall survival. Most patients were aged ≥ 65 years and were white; 91% to 92% had received at least three prior therapies.
Overall Survival and Other Outcomes
Median overall survival was 11.0 months in the cabozantinib group vs 9.8 months in the prednisone group (hazard ratio [HR] = 0.90, 95% confidence interval = 0.76–1.06, stratified log-rank P = .213).
Bone scan response at week 12 (secondary endpoint) was improved with cabozantinib (42% vs 3%, P < .001), as were outcomes in exploratory endpoints of radiographic progression-free survival (median = 5.6 vs 2.8 months, HR = 0.48, P < .001), circulating tumor cell (CTC) conversion (33% vs 6%), bone biomarkers, and symptomatic skeletal events (HR = 0.62, P < .001, for time to first event; 14% vs 21%). No differences between groups were observed for prostate-specific antigen (PSA) outcomes (median time to PSA progression = 4.2 vs 3 months, unstratified HR = 0.95, P = .639).
Grade 3 to 4 adverse events were more common in the cabozantinib group (71% vs 56%), as were treatment discontinuations due to adverse events (33% vs 12%). Serious adverse events occurred in 62% vs 53%.
The investigators concluded: “Cabozantinib did not significantly improve [overall survival] compared with prednisone in heavily treated patients with [metastatic castration-resistant prostate cancer] and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving [bone scan response, radiographic progression-free survival, symptomatic skeletal events], CTC conversions, and bone biomarkers but not PSA outcomes.”
The study was supported by Exelixis.
Matthew Smith, MD, PhD, of Massachusetts General Hospital Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
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