On September 22, 2017, the FDA granted accelerated approval to nivolumab (OPDIVO, Bristol-Myers Squibb) for the treatment of patients with hepatocellular carcinoma (HCC) previously treated with sorafenib.

CheckMate 040

Nivolumab for HCC received approval based on a 154-patient subgroup analysis of the Phase I/II, multicentre, open-label CheckMate 040 study (NCT01658878) in patients with HCC and Child-Pugh A liver cirrhosis refractory or intolerant to sorafenib.

Chronic Viral Hepatitis

The CheckMate 040 trial enrolled patients with either active viral hepatitis B (HBV, 31%) or viral hepatitis C (HCV, 21%) infections, though patients with active HBV/HCV co-infection or with hepatitis D virus infection were excluded.

Results

The confirmed overall response rate (ORR) was 14.3% (95% CI, 9.2-20.8) by blinded independent central review (RECIST 1.1). Three complete responses (CR) and 19 partial responses (PR) were observed, the duration of which ranged from 3.2 to 38.2+ months. Moreover, in 91% of the responses the duration was ≥6 months or longer; 55% of responses lasted ≥12 months.

Safety

Common adverse events (AEs), occurring in ≥20% of patients in nivolumab studies include fatigue, rash, musculoskeletal pain, pruritus, diarrhoea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia. An up-to-date list of AEs can be found here.

The AE profile of nivolumab in the CheckMate 040 was consistent with the general AE profile in patients with HCC. However, a higher incidence of transaminase and bilirubin elevations was reported; Grade 3 or 4 AST elevations occurred in 27 (18%) patients, Grade 3 or 4 ALT elevations were observed in 16 (11%) patients, and grade 3 or 4 bilirubin were found in 11 (7%) of patients. Eight (5%) patients experienced the immune-related AE (irAE) immune-mediated hepatitis requiring systemic corticosteroids.

Nivolumab prescribing information