Hepatocellular Carcinoma · Medical · Advanced / Metastatic · Pembrolizumab in advanced HCC; previously sorafenib-treated cohort and separate untreated cohort

KEYNOTE-224

Clinical question: In pembrolizumab in advanced hcc; previously sorafenib-treated cohort and separate untreated cohort, what is the efficacy and safety of the evaluated intervention?

Registry: NCT02702414 · One underlying study; aliases and follow-up publications consolidated.

Open-label, single-arm phase II study with two cohorts; one underlying trial, not two separate studies. Evidence cut-off: 13 November 2026.

Design, population and eligibility

Design / sample size

Open-label, single-arm phase II study with two cohorts; one underlying trial, not two separate studies.

Eligibility

Cohort 1: advanced HCC after sorafenib progression/intolerance. Cohort 2: systemic-therapy-naive advanced HCC.

Intervention

Pembrolizumab monotherapy.

Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles or progression/toxicity.

Comparator

As described in the study design; see primary publication.

Primary endpoint: ORR by RECIST 1.1 primary; DoR, PFS, OS and safety secondary.

Key efficacy outcomes

Cohort 1 (n=104): ORR 18.3%, median DoR 21.0 months, PFS 4.9 months, OS 13.2 months at long-term follow-up. Cohort 2 (n=51): ORR approximately 16%, median PFS 4.3 months and OS 16.9 months in the reported analysis.

Source-reported outcome: Cohort 1 (n=104): ORR 18.3%, median DoR 21.0 months, PFS 4.9 months, OS 13.2 months at long-term follow-up. Cohort 2 (n=51): ORR approximately 16%, median PFS 4.3 months and OS 16.9 months in the reported analysis.

Safety and treatment delivery

Cohort 1 grade 3–4 TRAEs 25%; grade 5 1%; immune-mediated hepatitis grade 3 in 3 patients.

Clinical interpretation and limitations

Single-arm activity signal; cannot establish comparative benefit. The two cohorts are parts of one phase II protocol and must not be counted as separate trials.

Interpret the reported hazard ratios in the context of the prespecified endpoint, statistical hierarchy, follow-up maturity, crossover/subsequent therapy and enrolled population. Median survival differences are not risk differences and must not be converted into NNT.

Absolute effect

No NNT/NNH is displayed unless an absolute event-risk difference at a clearly stated fixed timepoint can be calculated from reported trial data. Median survival differences and hazard ratios alone do not support an NNT. The visual above uses reported outcome data only.

Primary publication and follow-up

Primary publication

Registry / follow-up / authoritative source

Source-level verification status: primary publication identified and key quoted outcomes transcribed; where full-text toxicity or procedural details were not available, the page explicitly flags the limitation rather than inferring values.

Current-practice context · 13 November 2026

This page separates historical trial results from contemporary practice. Verify the applicable jurisdictional guideline, regulatory approval, biomarker assay, liver function, comorbidity and treatment availability before applying the evidence. NCCN Guidelines Insights are not a substitute for the full NCCN guideline.

Guideline/regulatory reconciliation and browser-rendered QA remain scheduled for the subsequent quality-control pass.