Study Finds No Recurrence-Free Survival Benefit of Adjuvant Sorafenib in Hepatocellular Carcinoma After Resection or Ablation
In the phase III STORM trial reported in The Lancet Oncology, Bruix et al found no benefit with adjuvant sorafenib (Nexavar) treatment in patients who had undergone resection or ablation for hepatocellular carcinoma.
Study Details
In this double-blind trial, 1,114 patients from 202 sites in 28 countries with complete radiologic response after resection (n = 900) or local ablation (n = 214) were randomly assigned between August 2008 and November 2010 to receive sorafenib 400 mg twice daily (n = 556) or placebo (n = 558) for a maximum of 4 years. Patients were stratified by curative treatment, geography, Child-Pugh status, and recurrence risk. The primary outcome was recurrence-free survival in the intent-to-treat population.
In the sorafenib and placebo groups, median age was 58 and 60 years (31% and 35% ≥ 65 years), 81% and 83% of patients were male, 63% and 61% were Asian and 33% and 34% were white, 81% in both had resection and 19% in both had ablation, recurrence risk was high in 46% and 45%, and Child-Pugh score was 5 in 77% of both groups and 6 in 20% and 19%.
No Benefit
Median follow-up for recurrence-free survival was 8.5 months in the sorafenib group and 8.4 months in the placebo group. Median recurrence-free survival was 33.3 months in the sorafenib group vs 33.7 months in the placebo group (hazard ratio [HR] = 0.940, P = .26). Subgroup analysis showed no significant effect of sorafenib treatment according to region, recurrence risk, Child-Pugh status, primary treatment, age, sex, or cause of underlying liver disease. Median time to recurrence was 38.5 vs 35.8 months (HR = 0.891, P = .12). Follow-up continues for overall survival. On first interim analysis, at median follow-up of 23.0 and 22.0 months, median overall survival had not been reached in either group (HR = 0.995, P = .48).
Adverse Events
Drug-related grade 3 and 4 adverse events occurred in 50% and 2% of the sorafenib group and in 9% and < 1% of the placebo group, with the most common in the sorafenib group being hand-foot skin reaction (28% vs < 1%) and diarrhea (6% vs < 1%). Dose modification occurred in 89% vs 38% of patients. Serious adverse events in sorafenib patients included hand-foot skin reaction (2%), abnormal hepatic function (< 1%), and fatigue (< 1%). There were four drug-related deaths in the sorafenib group (< 1%) and two in the placebo group (< 1%).
The investigators concluded: “Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation.”
Jordi Bruix, MD, of the University of Barcelona, is the corresponding author of The Lancet Oncology article.
The study was funded by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals. For full disclosures of the study authors, visit www.thelancet.com/journals/lanonc.
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