Cabozantinib and Zytiga make an exciting combination of drugs and expectations are high with the combined use of these drugs. Zytiga is already licensed for advanced metastatic prostate cancer and has to date shown encouraging activity in late stage disease. Cabozantinib targets the metastatic cancer and has been shown to decrease bone metastasis in Phase 2 trials. There is also a decrease in bone pain in patients receiving Cabozantinib. This drug targets the tyrosine kinase enzymes VEGFR and MET that are involved in angiogenesis and metastasis. A new trial has been announced that is to investigate the use of both these drugs in combination in a Phase 1 study. Since both these drugs have already been safely tested in Phase 2 and Phase 3 trials then the combination makes a worthwhile study.
Rationale for Combination Approach
Clinical and preclinical evidence suggest that inhibition of androgen receptor signaling (a consequence of treatment with the androgen synthesis inhibitor Zytiga) results in upregulation of a resistance mechanism mediated by MET signaling, which may contribute to the survival and invasiveness of prostate cancer cells. Cabozantinib is a potent inhibitor of MET, and may therefore enhance the activity of abiraterone by blocking this putative resistance mechanism. Additionally, the high level of activity that cabozantinib has demonstrated against both soft tissue and bone lesions in men with CRPC may complement the clinical activity of Zytiga.
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