Cabozantinib Improves PFS Over Sunitinib in Untreated Advanced RCC

A randomized phase II trial found that cabozantinib offers significantly better progression-free survival (PFS) over sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC), according to an announcement from the drug’s manufacturer, Exelixis. Cabozantinib was recently approved in the United States for previously treated advanced RCC.

The open-label CABOSUN trial included 157 RCC patients randomized to either cabozantinib 60 mg once daily (79 patients) or sunitinib 50 mg once daily (78 patients). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, and all were considered intermediate- or poor-risk.

Though detailed results are not yet available, the company reported that the trial has met its primary endpoint, with a significant and “clinically meaningful” improvement in PFS with cabozantinib compared with sunitinib.

“The positive outcome of CABOSUN is extremely exciting, as it marks the very first time that a therapy has shown a PFS benefit over standard-of-care first-line treatment sunitinib for patients with previously untreated advanced RCC,” said Toni K. Choueiri, MD, of Dana-Farber Cancer Institute and chair of the CABOSUN study, in a press release. “Based on these findings, cabozantinib may have the potential to become a new gold standard for previously untreated patients following their diagnosis with advanced kidney cancer.”

Cabozantinib is a multi-targeted tyrosine kinase inhibitor, with activity against MET; AXL; and VEGFR-1, -2, and -3. The US Food and Drug Administration granted approval for cabozantinib in April of this year, for treatment of advanced RCC in patients who had received prior antiangiogenic therapy.

That approval was based on results of the phase III METEOR trial, which compared cabozantinib with everolimus. METEOR was an open-label study that included 658 patients, and showed a 42% reduction in the rate of disease progression, as well as an improved objective response rate. The median overall survival was also better, at 21.4 months with cabozantinib compared with 16.5 months with sunitinib. Common adverse events included diarrhea, fatigue, and nausea, and 60% of cabozantinib patients required a dose reduction, compared with 24% of everolimus patients.