The oral vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (TKI) cabozantinib significantly improved overall survival, delayed disease progression, and improved objective response in patients with previously treated renal cell carcinoma (RCC), in contrast with everolimus, according to the results of the METEOR trial published recently in The Lancet Oncology.1
Based on these phase 3 results, the US Food and Drug Administration (FDA) approved cabozantinib in April for the treatment of patients with RCC who were previously treated with antiangiogenic therapy.
“It is very encouraging to see this overall survival benefit,” study researcher Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute in Boston, Massachusetts, told Cancer Therapy Advisor. “There has not ever been a single-agent oral TKI in renal cell cancer that has shown an overall survival benefit.”
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According to Dr Choueiri, cabozantinib differs from other approved TKIs for RCC because it targets multiple tyrosine kinases involved with the disease, including VEGF receptors MET and AXL.
METEOR
In the phase 3 METEOR trial, 658 patients with advanced or metastatic clear-cell RCC were randomly assigned to 60 mg cabozantinib once a day or 10 mg everolimus once a day. All patients had received at least 1 prior VEGF receptor TKI and had disease progression within 6 months of their most recent VEGF receptor TKI treatment. The primary endpoint of the trial was progression-free survival.
An initial analysis of data from the first 375 patients showed that cabozantinib significantly reduced the risk for disease progression or death by 42%, in contrast with everolimus (hazard ratio [HR], 0.58; 95% CI, 0.45-0.75; P < .0001). Although overall survival data were not mature at this point, there was a trend toward survival improvements among patients who were assigned cabozantinib.
Final analyses involved data with a median follow-up of about 19 months. At that time, patients assigned to cabozantinib had about a 5-month improvement in overall survival, in contrast with those assigned everolimus (21.4 versus 16.5 months; HR, 0.66; 95% CI, 0.53-0.83; P = .00026).
Patients assigned cabozantinib had a 49% improvement in the risk for progression (HR, 0.51; 95% CI, 0.41-0.62; P < .0001), and significantly greater objective response, in contrast with patients assigned everolimus (17% versus 3%; P < .0001).
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“One of the exciting things about cabozantinib is that it was looked at in a patient population who’ve had many prior therapies, and people wondered whether these patients just performed well, and whether that inflated results,” Naomi B. Haas, MD, associate professor of medicine at the Hospital of the University of Pennsylvania in Philadelphia, told Cancer Therapy Advisor. “The fact that the researchers looked at overall survival earlier on makes it easier to compare these results with those of drugs like nivolumab.”
