On March 10, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) for patients with hepatocellular carcinoma who have been previously treated with sorafenib.
Efficacy of the combination was investigated in cohort 4 of CheckMate 040, a multicenter, multiple cohort, open-label trial conducted in patients with hepatocellular carcinoma who progressed on or were intolerant to sorafenib. A total of 49 patients received nivolumab at 1 mg/kg in combination with ipilimumab at 3 mg/kg every 3 weeks for four doses, followed by single-agent nivolumab at 240 mg every 2 weeks until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate and duration of response as determined by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1. The overall response rate was 33% (n = 16; 95% confidence interval = 20%–48%), with 4 complete responses and 12 partial responses reported. Response duration ranged from 4.6 to 30.5+ months, with 31% of responses lasting at least 24 months.
The most common adverse reactions (≥ 20%) with the combination of nivolumab and ipilimumab were fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, decreased weight, and dizziness.
For patients with hepatocellular carcinoma, the recommended doses for the combination therapy are nivolumab at 1 mg/kg followed by ipilimumab at 3 mg/kg on the same day every 3 weeks for four doses; then, nivolumab at 240 mg every 2 weeks or 480 mg every 4 weeks.