Background
KEYNOTE-224: open-label, single-arm, non-randomized phase 2 trial in 104 patients with advanced hepatocellular carcinoma, Child-Pugh A, previously treated with sorafenib.
Interventions and follow up
Treatment: Pembrolizumab 200 mg IV every 3 weeks for up to 2 years
Primary endpoint: Objective response rate (RECIST 1.1, central review)
mFollow up: 12.3 months
Primary endpoint: Objective response rate (RECIST 1.1, central review)
mFollow up: 12.3 months
Results
ORR: 17%
mPFS: 4.9mo
mOS: 12.9mo
mPFS: 4.9mo
mOS: 12.9mo
Adverse events
Overall: Any-grade events 73%; grade ≥3 events 26%
Common any-grade: Fatigue 21%, increased AST 13%, pruritus 12%, diarrhea 11%, rash 10%
Grade ≥3: Increased AST 7%, fatigue 4%, increased ALT 4%
Common any-grade: Fatigue 21%, increased AST 13%, pruritus 12%, diarrhea 11%, rash 10%
Grade ≥3: Increased AST 7%, fatigue 4%, increased ALT 4%
Conclusions
Pembrolizumab produced durable objective responses and was well tolerated in advanced hepatocellular carcinoma previously treated with sorafenib.
Key Limitations
Single-arm, non-randomized design; no control; the confirmatory phase 3 KEYNOTE-240 narrowly missed its prespecified OS/PFS significance thresholds (later positive in KEYNOTE-394 in Asian patients).
Clinical Context
KEYNOTE-224 supported FDA accelerated approval of pembrolizumab for sorafenib-treated HCC (2018). ASCO/ESMO include pembrolizumab among later-line options; subsequent KEYNOTE-394 confirmed survival benefit in an Asian population.