Findings from the phase II KEYNOTE-224 trial investigating the use of pembrolizumab (Keytruda) in patients with advanced hepatocellular carcinoma who were previously treated with sorafenib (Nexavar) were presented by Zhu et al at the 2018 Gastrointestinal (GI) Cancers Symposium in San Francisco (Abstract 209).
Results showed an overall response rate of 16.3% (95% confidence interval [CI] = 9.8%–24.9%; n = 17/104) with pembrolizumab monotherapy. Data also include 6-month overall survival and progression-free survival rates.
“There continues to be a significant need for new options in the treatment of advanced hepatocellular carcinoma,” said Andrew Zhu, MD, PhD, lead investigator and Director of Liver Cancer Research at Massachusetts General Hospital Cancer Center. “The durable responses observed with pembrolizumab monotherapy in this difficult-to-treat cancer are encouraging.”
KEYNOTE-224 is a registrational, open-label phase II trial investigating pembrolizumab monotherapy in patients with advanced hepatocellular carcinoma who had previously received systemic therapy with sorafenib. The primary endpoint is overall response rate; secondary endpoints include duration of response, disease control rate, time to progression, progression-free survival, and overall survival.
Findings presented at the GI Cancers Symposium were based on data from 104 evaluable patients previously treated with sorafenib who received one or more doses of pembrolizumab (200 mg intravenous infusion on day 1 of each 3-week cycle for up to 35 administrations).
Data showed an overall response rate of 16.3% (95% CI = 9.8%–24.9%; n = 17/104), with a complete response rate of 1% (95% CI = 0.0%–5.2%) and a partial response rate of 15.4% (95% CI = 9.1%–23.8%). Overall response rate was similar across subgroups with different etiologies, including hepatitis B– and hepatitis C–positive patients. At the time of analysis, the median duration of response was 8.2 months (range = 2.3+ to 8.3+), with 94% of responses ongoing for 6 months or longer (calculated per Kaplan-Meier method).
The disease control rate was 61.5% (95% CI = 51.5%–70.9%; n = 64/104). The median progression-free survival was 4.8 months (95% CI, 3.4–6.6), with a 6-month progression-free survival rate of 43.1%. The median overall survival had not been reached at the time of analysis (95% CI = 9.4–not reached) with a 6-month overall survival rate of 77.9%.
The safety profile of pembrolizumab was consistent with that observed in previously reported studies. The treatment-related adverse events (any grade occurring in 10% or more of patients) were fatigue (12.5%), increased aspartate aminotransferase (9.6%), diarrhea (9.6%), and pruritus (21.2%). Grade 3 to 5 treatment-related adverse events occurred in 26 patients (25%), and there was 1 treatment-related death. Immune-mediated adverse events occurred in 2.9% of patients. Seven patients discontinued treatment due to treatment-related adverse events.
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