Hepatocellular Carcinoma · Medical · Advanced / Metastatic · Second-line pembrolizumab after sorafenib

KEYNOTE-240

Clinical question: In second-line pembrolizumab after sorafenib, what is the efficacy and safety of the evaluated intervention?

Registry: NCT02702401 · One underlying study; aliases and follow-up publications consolidated.

Phase III, randomized, double-blind, placebo-controlled trial; 413 patients. Evidence cut-off: 13 November 2026.

Design, population and eligibility

Design / sample size

Phase III, randomized, double-blind, placebo-controlled trial; 413 patients.

Eligibility

Advanced HCC previously treated with sorafenib; predominantly Child-Pugh A.

Intervention

Pembrolizumab + best supportive care versus placebo + best supportive care.

Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles.

Comparator

placebo + best supportive care.

Primary endpoint: OS and PFS primary endpoints with prespecified multiplicity-adjusted significance boundaries.

Key efficacy outcomes

Median OS 13.9 vs 10.6 months, HR 0.781 (95% CI 0.611–0.998), nominal p=0.0238. PFS final HR 0.718; median 3.0 vs 2.8 months. Trial did not cross prespecified statistical boundaries for OS/PFS.

Reported outcome

13.9

Comparator: 10.6. The bars are a simple display of the first reported pair only; consult the endpoint and time horizon above.

Safety and treatment delivery

Grade ≥3 AEs 52.7% vs 46.3%; grade ≥3 treatment-related AEs 18.6% vs 7.5%.

Clinical interpretation and limitations

Numerically favourable but formally negative primary study because multiplicity-adjusted boundaries were not met. Do not present nominal p-values as a positive phase III result.

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.