Background
Phase III double-blind RCT, N=1114 patients with HCC after curative-intent surgical resection (n=900) or local ablation (n=214) with complete radiological response. Patients were at intermediate-high risk of recurrence. Randomized 1:1 within a median of 6 weeks post-procedure. Stratified by curative treatment, geography, Child-Pugh status, and recurrence risk (BCLC 0/A).
Interventions and follow up
Arm A: Sorafenib 400 mg orally twice daily for up to 4 years
Arm B: Placebo twice daily for up to 4 years
Primary endpoint: Recurrence-free survival (RFS)
Follow-up: 8.5 mo (median RFS follow-up)
Arm B: Placebo twice daily for up to 4 years
Primary endpoint: Recurrence-free survival (RFS)
Follow-up: 8.5 mo (median RFS follow-up)
Results
RFS: 33.3 vs 33.7 mo, HR 0.94, 95% CI 0.78–1.13, P=.26
OS: NR (not reported at this analysis)
OS: NR (not reported at this analysis)
Adverse events
Grade 3–4 dermatologic/GI: hand-foot skin reaction 28% vs <1%, diarrhoea 6% vs <1% (sorafenib vs placebo).
Dose modification / deaths: dose modification in 89% of sorafenib patients vs 38% of placebo; drug-related deaths 4 (<1%) vs 2 (<1%).
Dose modification / deaths: dose modification in 89% of sorafenib patients vs 38% of placebo; drug-related deaths 4 (<1%) vs 2 (<1%).
Conclusions
Adjuvant sorafenib did not improve recurrence-free survival after curative resection or ablation of HCC. This large phase III trial definitively established that sorafenib is not effective in the adjuvant setting for HCC, despite its established role in advanced disease.
Key Limitations
The high rate of dose modification (89%) in the sorafenib arm may reflect inadequate tolerability, raising the possibility of underdosing in a proportion of patients. Recurrence was defined radiologically — pathologic confirmation was not required, which may introduce inconsistency across centres. The population included both resection and ablation patients, which differ in baseline recurrence risk, though subgroup analyses were not formally powered.
Clinical Context
STORM established that VEGFR/Raf inhibition with sorafenib does not reduce HCC recurrence after curative-intent treatment, likely because its mechanism does not address the tumor microenvironment mediating early relapse. Subsequent work with immune checkpoint inhibitors (IMbrave050, atezolizumab + bevacizumab adjuvant) showed benefit in this setting, shifting the adjuvant paradigm. STORM remains the historical reference for the null hypothesis in HCC adjuvant trials.