Cabozantinib Active in Castration-Resistant Prostate Cancer
(HealthDay News) – The orally bioavailable tyrosine kinase inhibitor cabozantinib (XL184) has clinical activity in men with castration-resistant prostate cancer (CRPC), according to a study published online Nov. 19 in the Journal of Clinical Oncology.
David C. Smith, MD, of the University of Michigan in Ann Arbor, and colleagues conducted a Phase 2 randomized discontinuation trial involving 171 men with CRPC to evaluate the activity of cabozantinib. Patients received 100mg of cabozantinib each day, and those with stable disease at 12-weeks were randomized to receive cabozantinib or placebo.
Based on the observed activity of cabozantinib, random assignment was stopped early. The researchers found that 72% of patients had regression in soft tissue lesions and 68% exhibited improvement on bone scan, including 12% with complete resolution. At 12 weeks, the objective response rate was 5%, and 75% exhibited stable disease. The median progression-free survival was 23.9 and 5.9 weeks for cabozantinib- and placebo-treated patients, respectively (hazard ratio, 0.12). In 57 percent of patients, there was a reduction of at least 50% in serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of Type I collagen. In a retrospective data review, bone pain was improved for 67% of patients, and narcotic use decreased by 56%. Fatigue, hypertension, and hand-foot syndrome were the most common Grade 3 adverse events.
"Cabozantinib has substantial antitumor activity in patients with advanced CRPC with manageable toxicity consistent with other tyrosine kinase inhibitors targeting multiple pathways," the authors write.
Several authors disclosed financial ties to pharmaceutical companies, including Exelixis, which manufactures cabozantinib and supported the study.