FDA Grants Accelerated Approval to Nivolumab for Hepatocellular Carcinoma Previously Treated With Sorafenib


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ON SEPTEMBER 22, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval to nivolumab (Opdivo) for the treatment of hepatocellular carcinoma in patients who have been previously treated with sorafenib (Nexavar). 

CheckMate 040 

APPROVAL WAS BASED on a 154-patient subgroup of CheckMate 040 (ClinicalTrials.gov Identifier NCT01658878), a multicenter, open-label trial conducted in patients with hepatocellular carcinoma and Child-Pugh A cirrhosis who progressed on or were intolerant to sorafenib. In addition to including patients without active hepatitis viral infection, the trial enrolled patients with either active hepatitis B virus (HBV, 31%) or hepatitis C virus (HCV, 21%) but not those with active coinfection with HBV and HCV or with hepatitis D virus infection. Patients received nivolumab at 3 mg/kg by intravenous infusion every 2 weeks. 

The confirmed overall response rate, as assessed by blinded independent central review using Response Evaluation Criteria in Solid Tumors 1.1, was 14.3% (95% confidence interval [CI] = 9.2%–20.8%), with 3 complete responses and 19 partial responses. Response duration ranged from 3.2 to 38.2+ months; 91% of responders had responses lasting 6 months or longer, and 55% had responses lasting 12 months or longer. 

Adverse Reactions 

COMMON ADVERSE REACTIONS occurring in greater than 20% of patients in nivolumab clinical trials include fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia. Adverse reactions occurring in patients with hepatocellular carcinoma in CheckMate 040 were similar to those previously reported in product labeling, with the exception of a higher incidence of elevations in transaminases and bilirubin levels. Treatment with nivolumab resulted in treatment-emergent grade 3 or 4 aspartate transaminase in 27 patients (18%), grade 3 or 4 alanine transferase in 16 patients (11%), and grade 3 or 4 bilirubin in 11 patients (7%). Immune-mediated hepatitis requiring systemic corticosteroids occurred in 8 patients (5%). 

The recommended nivolumab dose for hepatocellular carcinoma treatment is 240 mg every 2 weeks. ■


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