FDA Approves Cabozantinib for Renal Cell Carcinoma

Nick Mulcahy


April 26, 2016

The US Food and Drug Administration (FDA) has approved the oral therapy cabozantinib (Cabometyx, Exelixis) for the treatment of patients with advanced renal cell carcinoma (RCC) who have received previous antiangiogenic therapy.

The drug was approved in 2012 for the treatment of metastatic medullary thyroid cancer.

"Cabozantinib is distinct from other approved treatment options, as it targets multiple tyrosine kinases involved in the development of RCC, including MET, AXL, and three VEGF receptors," investigator Toni Choueiri, MD, from the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, said in a company press release.

"The approval of cabozantinib is wonderful news for physicians who are looking for a new option for their previously treated patients with advanced kidney cancer," he added.

The new approval was granted on the basis of results from the phase 3 METEOR trial, which compared cabozantinib with everolimus (Afinitor, Novartis), a standard of care for second-line RCC.

Median progression-free survival, the trial's primary outcome, was better with cabozantinib than with everolimus (7.4 vs 3.8 months; hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.45 - 0.74; P < .0001). These and other data were presented at the 2015 European Cancer Congress and simultaneously published in the New England Journal of Medicine (2015;373:1814-1823).

At that time, Dr Choueiri observed that the progression-free survival of 7.4 months was the longest ever seen in a second-line setting, as reported by Medscape Medical News.

Notably, overall survival data are now available from the METEOR trial. And median overall survival was also better with cabozantinib than with everolimus (21.4 vs 16.5 months; HR, 0.66; 95% CI, 0.53 - 0.83; P = .0003).

The efficacy profile of the drug is "highly compelling," summarized Dr Choueiri.

However, cabozantinib is not the first drug to show an overall survival benefit in this second-line setting.

In a phase 3 trial of patients with advanced RCC, median overall survival was better with the immunotherapy nivolumab (Opdivo, Bristol-Myers Squibb) than with everolimus (25.0 vs 19.6 months; HR, 0.73; = .002). On the basis of those results, nivolumab was approved for use in RCC in both the United States and Europe.

Various experts have voiced concern about the toxicity of cabozantinib, relative to that of nivolumab, including cabozantinib investigator Bernard Escudier, MD, from the Institut Gustave Roussy, Villejuif, France.

"Toxicity has been an issue" with cabozantinib, Dr Escudier said during a presscast from the Genitourinary Cancers Symposium 2016, as reported by Medscape Medical News.

The most common (frequency ≥ 25%) adverse reactions in cabozantinib-treated patients include diarrhea, fatigue, nausea, decreased appetite, hand–foot syndrome, high blood pressure, vomiting, weight loss, and constipation.

Dose reduction rates were 60% for cabozantinib and 24% for everolimus. The rate of treatment discontinuation because of adverse reactions was 10% in each group.

Dr Choueiri reports that his institution received a grant from Exelixis to conduct the clinical trial. Dr Escudier reports financial ties with multiple pharmaceutical companies, including Exelixis.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.