Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib

Abstract

Objective: Pembrolizumab, a PD-1 inhibitor, demonstrated anti-tumour activity and tolerability in patients treated with sorafenib and with advanced hepatocellular carcinoma in KEYNOTE-224. Longer-term efficacy and safety after ∼2.5 years of additional follow-up are reported. Patients and methods: Adults with confirmed hepatocellular carcinoma who experienced progression after or intolerance to sorafenib treatment received pembrolizumab 200 mg every 3 weeks for ≤35 cycles or until confirmed progression, unacceptable toxicity, withdrawal of consent or investigator decision. The primary end-point was objective response rate assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumours v1.1. The secondary end-points included duration of response, disease control rate, time to progression, progression-free survival, overall survival and adverse events. Results: Efficacy and safety were assessed in 104 patients. The median time from first dose to data cutoff was 45.1 months (range, 41.3–49.3). Objective response rate was 18.3% (95% CI: 11.4–27.1), and median duration of response was 21.0 months (range, 3.1 to 39.5+). Disease control rate was 61.5%, and median time to progression was 4.8 months (95% CI: 3.9–7.0). Median progression-free survival was 4.9 months (95% CI: 3.5–6.7) and median overall survival was 13.2 months (95% CI: 9.7–15.3). Of 104 patients, 76 (73.1%) patients reported treatment-related adverse events; most were low grade in severity (grade 3–4, n = 26 [25.0%]; grade 5, n = 1 [1.0%]). Immune-mediated hepatitis occurred in 3 patients (all grade 3). No viral-induced hepatitis flares occurred. Conclusions: After ∼2.5 years of additional follow-up, pembrolizumab continued to provide durable anti-tumour activity and no new safety concerns were identified. ClinicalTrials.gov identifier: NCT02702414.