STORM: A phase III randomized, double-blind, placebo-controlled trial of adjuvant sorafenib after resection or ablation to prevent recurrence of hepatocellular carcinoma (HCC)

4006^ Background: Sorafenib is a multikinase inhibitor with proven efficacy in unresectable HCC. We evaluated the efficacy and safety of adjuvant sorafenib for HCC. Methods: Patients who had undergone surgical resection or local ablation with curative intent and had an intermediate or high recurrence risk were eligible. Main inclusion criteria were Child-Pugh score 5–7, ECOG PS 0, and no residual disease confirmed by CT or MRI. Exclusion criteria included recurrent HCC, ascites, extrahepatic spread, macrovascular invasion, and prior systemic therapy for HCC. Patients were stratified by curative treatment, geographic region, recurrence risk, and Child-Pugh status and randomized 1:1 to treatment with sorafenib 400 mg orally twice a day or placebo for a maximum of 4 yrs. The primary endpoint was recurrence-free survival (RFS) by independent review. Secondary endpoints included time to recurrence (TTR) and overall survival (OS). Results: A total of 1114 patients were randomized (n=556 sorafenib; n=558 placebo). Baseline characteristics were balanced between groups. Median age was 59 yrs, 62% were Asian, 81% had resection, 97% were Child-Pugh A, and 46% had high recurrence risk. The analysis was based on a total of 464 RFS events. No differences in RFS, TTR, and OS were observed (Table). The sorafenib group had a shorter median treatment duration (12.5 vs 22.2 mos) and lower mean daily dose (578 vs 778 mg). Discontinuation rates with sorafenib were higher due to treatment-emergent adverse events (TEAE) (24% vs 7%) and consent withdrawal (17% vs 6%). Most common grade (Gr) 3–4 sorafenib TEAEs occurring more frequently vs placebo were hand-foot skin reaction (28%), hypertension (7%), and diarrhea (6%). Conclusions:The primary endpoint of the trial was not met. Adverse events are consistent with the known sorafenib safety profile and no new safety findings were observed. Clinical trial information: NCT00692770. Sorafenib Placebo Hazard Ratio (95% CI) P* Median, mos RFS 33.4 33.8 0.940 (0.780 – 1.134) 0.26 TTR 38.6 35.8 0.891 (0.735 – 1.081) 0.12 OS NR NR 0.995 (0.761 – 1.300) 0.48 TEAE, % All Gr 98 90 Serious 40 42 Gr 3–4 69 47 Gr 5 3 2 Drug-related, all Gr 94 46 Serious 9 3 Gr 5 <1 <1 *One sided; NR, not reached.