Cabozantinib success vs everolimus in Phase III study for renal cell carcinoma- Exelixis

Exelixis announced positive top-line results from the primary analysis of METEOR, the phase III pivotal trial comparing Cometriq (cabozantinib) to Afinitor (everolimus) in 658 patients with metastatic renal cell carcinoma (RCC) who have experienced disease progression following treatment with a VEGF receptor tyrosine kinase inhibitor (TKI). The trial met its primary endpoint of demonstrating a statistically significant increase in progression-free survival (PFS) in the first 375 randomized patients as determined by an independent radiology committee (IRC).

Cabozantinib reduced the risk of disease progression or death by 42 percent compared to the everolimus arm (hazard ratio [HR]=0.58, 95 percent CI 0.45-0.75, p<0.0001). Data pertaining to overall survival (OS) in the entire study population of 658 patients, a secondary endpoint of the trial, were immature at the data cutoff. A prespecified interim analysis, triggered by the primary analysis for PFS, showed a trend in OS favouring cabozantinib (HR = 0.67, unadjusted 95 percent CI 0.51 - 0.89; p=0.005). At the time of the interim analysis, the pre-specified p-value of 0.0019 to achieve statistical significance was not reached. The trial will continue to the final analysis of OS anticipated in 2016.

Comment: Cabozantinib is a tyrosine kinase inhibitor that targets the MET, VEGF receptor-2 and RET pathways.

Comment: On the same day of the announcement BMS announced that Opdivo (nivolumab) was found superior to Afinitor (everolimus) in overall survival in its Phase III renal cell carcinoma (CheckMate-025) study in such positive terms that the trial was halted.