Background
RESORCE: phase 3, double-blind, placebo-controlled trial in 573 patients with hepatocellular carcinoma, Child-Pugh A, BCLC stage B or C, who progressed on sorafenib (tolerated ≥400 mg/day), randomized 2:1 to regorafenib or placebo. Median prior sorafenib duration 7.8mo.
Interventions and follow up
Arm A: Regorafenib 160 mg/day, 3 weeks on / 1 week off
Arm B: Placebo
Primary endpoint: OS
mFollow up: 7.0 months
Arm B: Placebo
Primary endpoint: OS
mFollow up: 7.0 months
Results
OS: 10.6mo vs 7.8mo (Arm A vs B); HR 0.63, 95% CI 0.50-0.79; P<.0001
mPFS: 3.1mo vs 1.5mo (Arm A vs B)
mPFS: 3.1mo vs 1.5mo (Arm A vs B)
Adverse events
Overall: Treatment-related grade ≥3 events 50% vs 17% (Arm A vs B)
Dermatologic/vascular: Hand-foot skin reaction 52% vs 7%; hypertension 23% vs 5% (Arm A vs B)
GI/constitutional/hepatic: Diarrhea 33% vs 9%; anorexia 24% vs 6%; fatigue 29% vs 19%; increased bilirubin 19% vs 4% (Arm A vs B)
Dermatologic/vascular: Hand-foot skin reaction 52% vs 7%; hypertension 23% vs 5% (Arm A vs B)
GI/constitutional/hepatic: Diarrhea 33% vs 9%; anorexia 24% vs 6%; fatigue 29% vs 19%; increased bilirubin 19% vs 4% (Arm A vs B)
Conclusions
Regorafenib improved overall survival versus placebo in hepatocellular carcinoma progressing on sorafenib, the first agent to show benefit in the second-line setting.
Key Limitations
Enriched for sorafenib-tolerant patients (excluded those intolerant), limiting generalizability; Child-Pugh A only; predates first-line immunotherapy era.
Clinical Context
RESORCE led to FDA and EMA approval of regorafenib for sorafenib-treated HCC (2017). ASCO/ESMO include regorafenib among second-line options after first-line therapy in Child-Pugh A patients.
References
Bruix J et al, Lancet, 2016, PMID: 27932229
Llovet JM et al, NEJM, 2008 (SHARP), PMID: 18650514
Llovet JM et al, NEJM, 2008 (SHARP), PMID: 18650514