The U.S. Food and Drug Administration approved Opdivo® (nivolumab) in combination with Yervoy® (ipilimumab) for patients with hepatocellular carcinoma (HCC) who previously received Nexavar® (sorafenib).
The decision was based on results from the phase I/II, open-label, multi-cohort CheckMate-040 trial that included 49 patients with HCC who were previously treated with sorafenib. Patients received nivolumab 1 mg/kg intravenously (IV) and ipilimumab 3 mg/kg IV every three weeks for four doses, followed by nivolumab 240 mg every two weeks until disease progression or unacceptable toxicity.
Improved response with nivolumab plus ipilimumab
After a minimum follow-up of 28 months, 33% of patients (n=16) responded to treatment with nivolumab plus ipilimumab, including 8% (n=4) who experienced a complete response and 24% (n=12) with a partial response. The overall response rate was 35%.
Duration of responses ranged from 4.6 months to more than 30.5 months. Most responses (88%) lasted at least six months, 56% lasted at least 12 months, and 31% lasted at least 24 months.
The most common adverse events (AEs) were rash, pruiritus, musculoskeletal pain, cough, decreased appetite, fatigue, pyrexia, abdominal pain, nausea, dizziness, hypothyroidism, and decreased weight. More than half of patients (59%) who received the combination therapy experienced serious AEs, with 29% discontinuing treatment and 65% delating treatment. Serious AEs included pyrexia, diarrhea, anemia, increase aspartate aminotransferase, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis.