On January 22, 2021, the Food and Drug Administration approved  the combination of nivolumab and cabozantinib as first-line treatment for patients with advanced renal cell carcinoma (RCC).

Efficacy was evaluated in CHECKMATE-9ER (NCT03141177), a randomised, open-label trial in patients with previously untreated advanced RCC.

Patients were randomised to receive either nivolumab 240 mg over 30 minutes every 2 weeks in combination with cabozantinib 40 mg orally once daily (n=323) or sunitinib 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 (PFS), overall survival (OS) and confirmed overall response rate (ORR) for patients treated with nivolumab plus cabozantinib compared with those who received sunitinib.

Median PFS per blinded independent central review (BICR) was 16.6 months versus 8.3 months; HR 0.51 (95% CI: 0.41, 0.64). Median OS was not reached in either arm; HR 0.60 (95% CI: 0.40, 0.89). Confirmed ORR per BICR 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 diarrhoea, 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 240 mg every 2 weeks (30-minute intravenous infusion) or 480 mg every 4 weeks (30-minute intravenous infusion) in combination with cabozantinib 40 mg orally once daily without food until disease progression or unacceptable toxicity.

View full prescribing information for nivolumab here.
View full prescribing information for cabozantinib here.

Source: FDA