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WASHINGTON -- The FDA on Friday for treating advanced renal cell carcinoma (RCC) in the first-line setting.

Support for approval came from CheckMate-9ER, a phase III trial that randomized 651 previously untreated patients with advanced RCC to either sunitinib (Sutent) alone or the combination of nivolumab, a PD-1-directed checkpoint inhibitor, plus the tyrosine kinase inhibitor cabozantinib, until disease progression or unacceptable toxicity.

"This combination of cabozantinib and nivolumab significantly improved key efficacy measures compared to sunitinib -- progression-free survival, overall survival, and objective response rate -- while showing a low rate of treatment discontinuations due to side effects," investigator Toni Choueiri, MD, of Dana-Farber Cancer Institute in Boston, said in a .

Overall survival was significantly improved with nivolumab (240 mg every 2 weeks delivered intravenously) plus oral cabozantinib (40 mg daily) compared with oral sunitinib at standard dosing, with a median not reached in either study arm (HR 0.60, 95% CI 0.40-0.89).

Median progression-free survival doubled with the combination, at 16.6 months versus 8.3 months with sunitinib (HR 0.51, 95% CI 0.41-0.64), and the overall response rate reached 55.7% with the two-drug combination versus 27.1% with sunitinib.

"The therapeutic benefit demonstrated in CheckMate-9ER and quality of life measures explored emphasize the role of this combination for patients with advanced kidney cancer," added Choueiri. "With this important FDA approval, the combination is poised to become a standard in newly diagnosed metastatic kidney cancer."

Common toxicities with the combination included abdominal or musculoskeletal pain, cough, diarrhea, dysgeusia, fatigue, hepatotoxicity, hand-foot syndrome, hypertension, hypothyroidism, nausea, rash, reduced appetite, stomatitis, and upper respiratory tract infection. In all, 20% of patients treated with nivolumab-cabozantinib stopped one of the treatments, or both, due to toxicity.

The combination joins three other first-line options in advanced RCC: ipilimumab (Yervoy) plus nivolumab for intermediate- or high-risk patients, and pembrolizumab (Keytruda) plus axitinib (Inlyta) or for all risk groups.

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