Second-line treatment with nivolumab was well tolerated and associated with encouraging preliminary activity among patients with advanced hepatocellular carcinoma, according to an interim analysis presented at the European Society for Medical Oncology (ESMO) 2016 Congress.1
Patients with advanced hepatocellular carcinoma who fail sorafenib therapy typically receive best supportive care, though this approach is associated with a median overall survival of up to only 7 to 8 months. Researchers therefore evaluated the activity and tolerability of second-line nivolumab, a PD-1 inhibitor, among patients with advanced liver cancer previously treated with sorafenib.
For the phase 1/2 CheckMate-040 study (A Study to Evaluate the Effectiveness, Safety and Tolerability of Nivolumab and the Combination Nivolumab Plus Ipilimumab in Patients With Advanced Liver Cancer; ClinicalTrials.gov Identifier: NCT01658878), investigators enrolled 48 patients with Child-Pugh scores of 7 or lower into a dose-escalation phase and 214 with scores of 6 or lower into a dose expansion phase. Patients who failed, refused, or were intolerant of sorafenib received nivolumab for up to 2 years.
The overall response rate in the dose escalation phase was 15% (95% CI, 6-28) and 16% (95% CI, 12-22) in the dose expansion phase, which included 4 complete responses in total.
In the dose escalation phase, median duration of response was 17 months (95% CI, 6-24) and median overall survival was 14.3 months (95% CI, 9.6-18.9).
In the dose expansion phase, the 6- and 9-month overall survival rates were 82.5% and 70.8%, respectively. Rates were similar between sorafenib-naive/intolerant patients and those who failed sorafenib.
Responses occurred regardless of hepatocellular etiology and PD-L1 expression.
The most common treatment-related adverse events were fatigue, pruritus, rash, and diarrhea, with the common grade 3 to 4 events including increased aspartate transaminase (AST), increased lipase, increased alanine transaminase (ALT), and increased amylase.
- Melero I, Sangro B, Yau T, et al. Safety and preliminary efficacy of nivolumab (nivo) in patients (pts) with advanced hepatocellular carcinoma (aHCC): Interim analysis of the phase 1/2 CheckMate-040 study. Paper presented at: European Society for Medical Oncology (ESMO) 2016 Congress; October 7-11, 2016; Copenhagen, Denmark.