Since VEGF signalling is involved with the growth and spread of metastases VEGFR inhibitors have potential for treating all types of solid tumours that are prone to metastasis such as lung cancer, breast cancer, and prostate cancer. The potential utility of Tivozanib in treating prostate cancer has been somewhat overlooked and no clinical trials have been started yet, but this drug would make a good combination with Zytiga (i.e. Tivozanib Zytiga Combo) for treating metastatic prostate cancer, since both drugs are well tolerated and would combine well together. The VEGFR-2 inhibitor Cabozantinib in combination with Zytiga is currently in clinical trials and the results against resolution of bone mets look impressive.
Molecular structure of Tivozanib shows that it is a very well designed drug. The quinazoline group mimics adenosine and binds into the ATP binding site of the VEGF receptor with the chloroary side chain fitting into the hydrophobic binding pocket.
The next generation of potential blockbusters in oncology will come from the new "inibs", tyrosine kinase inhibitors that are targetted against specific kinases involved in cancer survival. This new generation of oncology drugs includes Ibrutinib (PCYC), Cabozantinib (EXEL), and Tivozanib (AVEO), all of which are showing exciting clinical activity. The first generation of "inibs" are already blockbusters such as Imatinib otherwise known as Glivec (NVS).
The Phase 3 clinical trials of Tivozanib are against kidney cancer, and compared this drug with the current VEGFR inhibitor Sorafenib. There was no increase in overall survival (OS) with patients treated with Tivozanib compared with Sorafenib, but there was a statistically significant increase in progression free survival (PFS) which was the primary goal of the trial. This trial also demonstrated the safety of Tivozanib which showed that it was a well tolerated drug with few side effects and importantly had an improved safety profile when compared to Sorafenib.
Taken together the improvement in progression free survival and good safety profile of Tivozanib make this a useful agent in oncology for treating kidney cancer and warrants regulatory approval.
