Cabozantinib Tops Everolimus in Advanced RCC, Regardless of MET Expression

Expression of MET as measured by immunohistochemistry was not associated with any difference in the performance of cabozantinib as compared with everolimus in patients with advanced renal cell carcinoma (RCC), according to a new analysis. Cabozantinib outperformed everolimus on several outcomes regardless of MET expression levels.

The METEOR trial showed that cabozantinib was better than everolimus in patients who progressed after treatment with VEGFR-targeted therapy; the final results of that trial were published in Lancet Oncology earlier in 2016. The new analysis of whether MET expression affected these results was presented by Thomas Powles, MD, of Barts Cancer Institute in London, at the 15^th International Kidney Cancer Symposium, held November 4–5 in Miami, Florida.

“The key to this is individuals who took part in the trial had archive tissue that was taken,” Powles said. That tissue was stained using SP44 antibody to determine MET expression; 15% of patients were deemed MET high (51 cabozantinib patients, 50 everolimus patients), 47% were MET low (150 cabozantinib, 182 everolimus), and 37% were MET unknown (129 cabozantinib, 116 everolimus). Powles noted that the numbers included were relatively small, adding that “when we start to get these kinds of numbers, one gets slightly nervous about overinterpreting results.”

Progression-free survival was better with cabozantinib in each of the three MET expression groups. In the MET-high patients, the hazard ratio (HR) for progression with cabozantinib was 0.38 (95% CI, 0.23–0.62). In the MET-low patients, it was 0.57 (95% CI, 0.43–0.70), and it was also still better in MET-unknown patients.

Overall survival in MET-high patients was also better with cabozantinib, with an HR of 0.55 (95% CI, 0.41–0.99). In MET-low patients, the HR was 0.72 (95% CI, 0.52–1.00). However, Powles noted that “the numbers are too small and the patient imbalance too powerful to take any dramatic conclusion from that.”

The same applied to tumor responses, he said, and cabozantinib did outperform everolimus again regardless of MET expression level.

“In these key efficacy endpoints, we’ve shown outperformance of cabozantinib compared to everolimus irrespective of MET expression,” Powles concluded. He noted that the tissue resource from the METEOR trial could be valuable in future analyses, including using other approaches than immunohistochemistry such as gene expression profiles, to determine if responses and outcomes do vary by other markers.