Zhu AX, et al. - In patients with advanced hepatocellular carcinoma, pembrolizumab was tested with respect to its efficacy and safety as a treatment option. Researchers found that patients with advanced hepatocellular carcinoma who had previously been treated with sorafenib were benefitted by pembrolizumab, which also showed good tolerability in these patients. Overall, pembrolizumab may be a treatment option for these patients.

Methods

• A non-randomized, multicenter, open-label, phase 2 trial, the KEYNOTE-224, was conducted at 47 medical centers and hospitals across ten countries.
• The following features were required to be present in patients for inclusion in the study: pathologically confirmed hepatocellular carcinoma; previous treatment with sorafenib and were either intolerant to this treatment or showed radiographic progression of their disease after treatment; an Eastern Cooperative Oncology Group performance status of 0–1; adequate organ function, and Child-Pugh class A.
• Intravenous administration of 200 mg pembrolizumab was administered for every 3 weeks for about 2 years or until disease progression, unacceptable toxicity, patient withdrawal, or investigator decision.
• Objective response, defined as the share of patients with complete or partial response in all patients who received at least one dose of pembrolizumab was the primary objective.
• In all treated patients, safety evaluation was carried out.

Results

• Screening of 169 patients with advanced hepatocellular carcinoma was carried out between June 7, 2016, and Feb 9, 2017, of whom 104 eligible patients were enrolled and treated.
• Pembrolizumab was still being administered to 17 (16%) patients as of data cutoff on Feb 13, 2018.
• An objective response was observed in 18 (17%; 95% CI 11–26) of 104 patients.
• One (1%) complete and 17 (16%) partial responses were reported that were considered the best overall responses.
• Meanwhile, stable disease was detected in 46 (44%) patients, progressive disease in 34 (33%).
• The occurrence of treatment-related adverse events was reported in 76 (73%) of 104 patients, serious adverse events were reported in 16 (15%) patients.
• A total of 25 (24%) of the 104 patients experienced grade 3 treatment-related events; the most common were increased aspartate aminotransferase concentration in seven (7%) patients, increased alanine aminotransferase concentration in four (4%) patients, and fatigue in four (4%) patients.
• Researchers also reported one (1%) grade 4 treatment-related event of hyperbilirubinaemia, as well as one death associated with ulcerative esophagitis, attributed to treatment.
• Occurrence of immune-mediated hepatitis was reported in three (3%) patients, but there were no reported cases of viral flares.