On January 22, 2021, the FDA approved the combination of nivolumab (Opdivo; Bristol Myers Squibb), an immune checkpoint inhibitor, and cabozantinib (Cabometyx; Exelixis), a tyrosine kinase inhibitor, for the first-line treatment of patients with advanced renal-cell carcinoma.
“With this important FDA approval, the combination is poised to become a standard in newly diagnosed metastatic kidney cancer,” Toni Choueiri, MD, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute; and Jerome and Nancy Kohlberg Chair and Professor of Medicine, Harvard Medical School, Boston, MA, said in a press release.
The approval was based on results of an open-label, randomized, phase 3 trial that compared nivolumab in combination with cabozantinib (N = 323) versus sunitinib (N = 328) in patients with advanced or metastatic renal-cell carcinoma.
The primary end point of the trial was progression-free survival. Secondary end points included overall survival and ORR. Median follow-up was 18.1 months.
At a median follow-up of 18.1 months, the median progression-free survival was 16.6 months with nivolumab plus cabozantinib versus 8.3 months for sunitinib. The median overall survival had not yet been reached in either arm, translating to a 40% reduction in the risk for death with the nivolumab plus cabozantinib arm (hazard ratio, 0.60; 95% confidence interval, 0.40-0.89; P = .001). The ORR with nivolumab plus cabozantinib versus sunitinib was 55.7% and 27.1%, respectively (P <.0001).
The most common (≥20%) adverse reactions of any grade in patients receiving nivolumab plus cabozantinib were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), cough (20%), and upper respiratory tract infection (20%).
The rate of serious adverse reactions was similar between the 2 treatment arms. All-cause adverse reactions leading to discontinuation of either nivolumab or cabozantinib occurred in 19.7% of patients, with 6.6% discontinuing just nivolumab, 7.5% discontinuing just cabozantinib, and 5.6% discontinuing the combination.
The FDA previously granted the combination of nivolumab plus cabozantinib a priority review.