Approval accelerated approval of pembrolizumab (Keytruda, Merck) for the treatment of patients with hepatocellular carcinoma (HCC) who had previously received sorafenib (Nexavar, Bayer). Keytruda is also approved in combination with carboplatin and paclitaxel or nab-paclitaxel for first-line treatment of metastatic squamous non-small cell lung cancer.
FDA is based on single-arm, open label KEYNOTE-224 test results. The trial included 104 patients (median age, 68 years; 83% males; 81% whites; 14% Asians) with HCC who experienced disease progression or against Intolerance. The ECOG performance status of all patients was 0 (61%) or 1 (39%), which was Child-Pugh grade A liver function impairment. In addition, 21% were seropositive for hepatitis B virus, 25% were seropositive for hepatitis C virus, and 9% were seropositive. 64% of patients have extrahepatic disease, 17% have vascular invasion, and 9% have both. Patients received pembrolizumab 200 mg every 3 weeks for 24 months, or until disease progression or unacceptable toxicity. Objective response rate and duration of response were used as the main efficacy results. The median exposure time of pembrolizumab was 4.2 months. The ORR reported by the researchers was 17% (95% CI, 11-26), including a 1% complete response rate and a 16% partial response rate. Of the 18 patients who obtained the response, 16 (89%) were still effective for at least 6 months, and 10 (56%) were still effective for at least 12 months.
The adverse effects of Pembrolizumab-treated HCC patients appeared to be similar to those observed in other studies of меланом or NSCLC, but the incidence of ascites increased (grade 3/4, 8%) and immune-mediated hepatitis (2.9%). Grade 3 or 4 laboratory abnormalities that occurred more frequently in the KEYNOTE-224 trial included elevated alanine aminotransferase (20%), elevated aspartate aminotransferase (9%) and hyperbilirubinemia (10 %).
Keytruda’s approval provides a new treatment option for patients with hepatocellular carcinoma who have received sorafenib treatment.
