Cabozantinib Active in Advanced Castration-Resistant Prostate Cancer


A phase II study indicates that cabozantinib has strong antitumor activity in advanced castration-resistant prostate cancer and improves bone scan lesions.

Results from a phase II study indicate that the oral tyrosine-kinase inhibitor cabozantinib has strong antitumor activity in men with advanced castration-resistant prostate cancer, improving bone scan lesions in a majority of men while maintaining a manageable toxicity profile.

Chemical structure of cabozantinib

“These results are completely unprecedented and suggest a new avenue of research in the treatment of this disease,” said David C. Smith, MD, professor of medicine and urology at the University of Michigan. Smith and colleagues published the results of this phase II study in the Journal of Clinical Oncology.

A prior phase I study of cabozantinib found that the drug has activity against MET and VEGF receptor 2, which both play important roles in the progression of castration-resistant prostate cancer. More importantly, prior research showed that the drug blocked the progression of osteolytic and osteoblastic lesions, a relevant activity given that bone is the most prevalent location for metastases in prostate cancer.

For this phase II discontinuation study, 171 enrolled patients were given 100 mg of cabozantinib daily. Study plan indicated that those patients with stable disease at 12 weeks would be randomly assigned to continue cabozantinib or placebo. The researchers were looking for a response in the form of progression-free survival and objective response rate at 12 weeks.

At 12 weeks, 5% of patients had partial response and 75% had stable disease. Eleven percent of patients had progressed. Due to the overall response to cabozantinib, random assignment was ceased after 31 patients were randomly assigned.

Patients assigned to cabozantinib had a progression-free survival of 23.9 weeks compared with 5.9 weeks for those patients assigned to placebo (P < .001).

“The main finding of this study is that cabozantinib has significant activity against prostate cancer,” said Smith. “The surprising aspect of this activity is the marked response seen in bone scans. These effects were dramatic and were seen in the majority of men treated, and this effect has not been seen previously in the treatment of prostate cancer.”

The researchers conducted a post hoc analysis of the effects of the study drug on bone scan. At baseline, 149 patients had evidence of bone metastases and 78% of these patients had at least one follow-up bone scan. Overall, 68% of patients had disease improvement as evidenced by bone scan with a complete resolution of disease in 12% of patients. In addition, 67% of patients reported an improvement in bone pain.

“Cabozantinib shows promise as an agent to use in the treatment of men with prostate cancer,” Smith said. “Further, the results suggest that the c-Met and VEGF pathways are important in the progression of prostate cancer and are therapeutic targets in this disease.”

Trials are now ongoing to determine cabozantinib’s effect on survival and to define the mechanism by which it works, according to Smith.

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