On January 22, the U.S. Food and Drug Administration (FDA) approved the combination of nivolumab (Opdivo) and cabozantinib (Cabometyx) as first-line treatment for patients with advanced renal cell carcinoma.
Efficacy was evaluated in CheckMate 9ER, a randomized, open-label trial in patients with previously untreated advanced renal cell carcinoma. Patients were randomly assigned to receive either nivolumab at 240 mg over 30 minutes every 2 weeks in combination with cabozantinib at 40 mg orally once daily (n = 323) or sunitinib at 50 mg orally daily for the first 4 weeks of a 6-week cycle (4 weeks on treatment, followed by 2 weeks off; n = 328).
The trial demonstrated a statistically significant improvement in progression-free survival, overall survival, and confirmed overall response rate for patients treated with nivolumab plus cabozantinib compared with those who received sunitinib. Median progression-free survival per blinded independent central review was 16.6 months vs 8.3 months (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.41–0.64). Median overall survival was not reached in either arm (HR = 0.60, 95% CI = 0.40–0.89). Confirmed overall response rate per blinded independent central review was 55.7% and 27.1% in the nivolumab plus cabozantinib and sunitinib arms, respectively.
The most common adverse reactions (≥ 20%) in patients receiving the combination of nivolumab and cabozantinib were diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysaesthesia syndrome, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.
The recommended dose is nivolumab at 240 mg every 2 weeks (30-minute intravenous infusion) or at 480 mg every 4 weeks (30-minute intravenous infusion) in combination with cabozantinib at 40 mg orally once daily without food until disease progression or unacceptable toxicity.