We are again looking at a potentially new block buster drug to treat men with advanced prostate cancer whose cancer has become castrate resistant. This potential drug seems to have clinical activity in both soft tissue and bone mets. This investigational drug is called Cabozantinib (XL184).

It is a tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. In the trial 184 was administered orally (by mouth) at a dosage of 100 mg each day.

The researchers conducted a phase II discontinuation trial with an expansion cohort. The trial involved taking men with stable disease per RECIST at 12 weeks and randomly assigning them to either cabozantinib or placebo. The primary end points were objective response rate at 12 weeks and progression-free survival (PFS) after random assignment.

The trial enrolled one hundred seventy-one men (171) with advanced prostate cancer that had become castrate resistant. The trial was halted early based on the observed activity of cabozantinib. Seventy-two percent of men had regression in soft tissue lesions, whereas 68% of evaluable patients had improvement on bone scan, including the complete resolution in 12% of the men receiving the trial treatment.

The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty-one men with stable disease at week 12 were randomly assigned.

Median progression free survival was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and only 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with men given placebo (hazard ratio, 0.12; P < .001). On a retrospective review of the data, bone pain improved in 67% of evaluable men, with a decrease in narcotic pain killer use in 56% of the men. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%). This exciting trial has shown that Cabozantinib has significant clinical activity in men with CRPC. It causes the reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turn over markers, pain and the need for narcotics. Cabozantinib (XL184) will hopefully quickly go into phase III trials. It is a potential treatment that is clearly On the Horizon. The researchers who have been involved with this trial are:
David C. Smith?, Matthew R. Smith, Christopher Sweeney, Aymen A. Elfiky, Christopher Logothetis, Paul G. Corn, Nicholas J. Vogelzang, Eric J. Small, Andrea L. Harzstark, Michael S. Gordon, Ulka N. Vaishampayan, Naomi B. Haas, Alexander I. Spira, Primo N. Lara Jr, Chia-Chi Lin, Sandy Srinivas, Avishay Sella, Patrick Schöffski, Christian Scheffold, Aaron L. Weitzman and Maha Hussain

Joel T Nowak, M.A., M.S.W.