Pembrolizumab Monotherapy in Sorafenib-Treated and Treatment-Naïve Advanced Hepatocellular Carcinoma: Long-Term Follow-up of the Open-Label, Phase II KEYNOTE-224 Study

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: Median OS: 13.2 months (sorafenib-treated) vs 16.9 months (treatment-naïve)

• Primary Outcome: Objective response rate per RECIST v1.1 by blinded independent central review

• Nnt Or Sensitivity: 48-month OS rates: 17% (sorafenib-treated) and 20% (treatment-naïve)

• Confidence Interval: 95% CI: 9.7-15.3 months (cohort 1), 8.3-23.1 months (cohort 2)

Clinical Application

Pembrolizumab is readily available with established administration protocols; requires oncology expertise and immune-related adverse event monitoring Pembrolizumab is PBS-listed for various cancers; TGA-approved for HCC. Results support current RACGP referral guidelines for advanced HCC to medical oncology Adults with advanced hepatocellular carcinoma suitable for immunotherapy, both treatment-naïve and post-sorafenib

Abstract

PURPOSE: In the phase II KEYNOTE-224 study, pembrolizumab showed durable antitumor activity and manageable safety in participants with sorafenib-treated (cohort 1) or treatment-naïve (cohort 2) advanced hepatocellular carcinoma (HCC). We present data after a median follow-up of ∼7 years for cohort 1 and ∼5 years for cohort 2. PATIENTS AND METHODS: Adults with advanced HCC received pembrolizumab 200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity for ≤35 cycles. The primary endpoint was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. RESULTS: Overall, 155 participants received ≥1 dose of pembrolizumab (cohort 1, n = 104; cohort 2, n = 51). The median follow-up was 83 months (range, 79.3-87.3) for cohort 1 and 58.8 months (range, 55.3-60.8) for cohort 2. The median OS was 13.2 months [95% confidence interval (CI), 9.7-15.3] and 16.9 months (95% CI, 8.3-23.1), respectively; 24- and 48-month OS rates were 31%/17% and 34%/20%, respectively. The median PFS was 4.9 months (95% CI, 3.5-7) and 4.3 months (95% CI, 2.1-7.8), respectively. Treatment-related adverse events occurred in 76 participants [73.1%; grade 3-5, 27 (26%)] in cohort 1 and 28 participants [54.9%; grade 3-5, 8 (15.7%)] in cohort 2. CONCLUSIONS: Pembrolizumab continued to show durable response and manageable safety in participants with advanced HCC with or without prior systemic therapy, with long-term effects on OS lasting beyond 48 months in some participants despite receiving study treatment for ≤2 years.

References

1. 1.Finn, R. S., Kudo, M., Borbath, I., Edeline, J., Cattan, S., van Vlierberghe, H., Verslype, C., Palmer, D., Stål, P., Ogasawara, S., Vogel, A., Chan, S. L., Knox, J. J., Daniele, B., Odeleye-Ajakaye, A., Hatogai, K., Siegel, A. B., Cheng, A. L., & Van Laethem, J. L. (2026). Pembrolizumab monotherapy in sorafenib-treated and treatment-naïve advanced hepatocellular carcinoma: Long-term follow-up of the open-label, phase II KEYNOTE-224 study. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-25-3528