How We Know What Drugs Might Work In Combination With Each Other – Bringing The Next Big Breakthrough in Prostate Cancer Treatment

Many of the posts that I have written discussed the need for evaluating our current advanced prostate cancer drugs in both combinations and their sequencing. We have a number of new drugs, but we don’t understand how best to sequence them, or whether or not some drugs would do better and extend life by taking them in combination. Actually, my last post mentioned that perhaps the next big breakthrough will not be a new drug approval, but be a better understanding how to better sequence and combine the currently approved drugs. Understanding how we get to effective clinical trials, which [...]

Cabozantinib Fails In the Phase III COMET-1 Trial

The pharmaceutical company Exelixis has announced that their experimental treatment, cabozantinib has failed the Phase III clinical trial for men with metastatic castration-resistant prostate cancer (mCRPC). In the trial the experimental treatment cabozantinib was compared to the drug prednisone. In the trial known as COMET-1, Cabozantinib, a tyrosine kinase inhibitor, did not meet its primary endpoint of demonstrating a statistically significant increase in overall survival (OS) for men compared to prednisone.   The trial compared the effectiveness of cabozantinib and prednisone in 960 men with mCRPC whose disease progressed after treatment with docetaxel as well as abiraterone and/or enzalutamide. Men were [...]

On the Horizon – Targeting Bones in the Treatment of Advanced Prostate Cancer

Osteoblasts and osteoclasts are the process that the body uses to breakdown old bone and then to rebuild it with new bone. c-Met is a tyrosine kinase expressed by osteoblasts and osteoclasts, and overexpressed by prostate cancer cells. This over expression leads to the eventual development of bone metastases. The experimental treatment known as Cabozantinib (XL-184) is a c-Met and vascular endothelial growth factor receptor-2 inhibitor. It has been tested in men with mCRPC yielding impressive results from a phase II study that enrolled 171 men. The results showed n a partial or complete improvement in the bone scans in [...]


Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. It is designed to target the men with castration resistant prostate cancer (CRPC). Results from a phase II randomized discontinuation trial with an expansion cohort of XL184 have recently been released. The trial included men with castrate resistant prostate cancers who were given 100 mg of XL185 daily. The men who demonstrated stable disease at 12 weeks were randomly assigned to either cabozantinib or to placebo. The trial’s primary end points were objective response rate at 12 weeks and progression-free [...]