Multicenter Phase II Clinical Trial of Sorafenib Combined with Transarterial Chemoembolization for Advanced Stage Hepatocellular Carcinomas (Barcelona Clinic Liver Cancer Stage C): STAB Study

Summary

A phase II non randomized open label multicenter study designed to evaluate the efficacy and safety of combining Sorafinib with conventional Trans arterial chemoembolization (TACE) in patients with Barcelona Clinic Liver Cancer Stage C hepatocellular cancer(HCC) is described in this paper. Primary end point was completion rate of the treatment protocol defined as 2 months of treatment with Sorafinib after TACE. Secondary end points of the study included objective response rate, disease control rate, overall survival, progression free survival and incidence of adverse effects. Sorafinib 400 mg daily was administered after 4 weeks of lobar/segmental/sub segmental conventional TACE with lipoidol combined with any of the following 5 drugs: epirubicin, doxorubicin, cisplatin, miraplatin, mitomycin C. Dose interruptions and reductions were allowed when drug toxicity developed. 32 patients were enrolled, 1 was excluded as tumor was cholangiohepatoma and not HCC. All 31 patients were followed for a year or until death. 28 (90.3%) patients completed the protocol, 1 refused treatment with Sorafinb, 2 dropped out due to intolerance/ drug toxicity. Median number of TACE were 2, Sorafinib interruptions was required in 77.4% and dose reduction in 67.7%. Complete, partial response, stable disease and progressive disease were noted in 9.7,67.7,12.9 and 9.7% respectively using the mRECIST criteria. Objective response rate was 77.4% and disease control rate was 90.3%. Median overall survival and progression free survival were 17.3 months and 5.4 months respectively. Tumor response rate by mRECIST (P=0.42) and serum AFP(P=0.01) were the only significant prognostic factors that affected survival in multivariate analysis. The most common grade 3 or 4 AEs were increased AST (54.8% 17/31), increased ALT (45.2%, 14/31), hypertension (22.6%, 7/31), thrombocytopenia(19.4%, 6/31), increased amylase (9.7%, 3/31), and hand-foot syndrome (9.7%; 3 of 31) during the entire period of combination therapy. 

Fig 1 Kaplan Meier curve showing overall survival of patients included in the study

Commentary

This was a much needed study evaluating combination therapy in advanced disease. While the primary end point was achieved in over 90%, the tolerability of Sorafinib after TACE was variable with only 9.7% of the patient sticking to the original dosage regime.

Subgroup analysis of the SHARP and Asia-Pacific trials showed a median overall survival of 5.6-9.7 months in advanced stage HCC with Sorafinib monotherapy. The present study demonstrates an overall survival of 17.3 months compared to these trials. However, it should be noted that SHARP and Asia-Pacific trials were much larger trials with a more advanced patient population and more advanced BCLC stage than the presented study. The authors attribute the improved survival to patient selection and exclusion of patients with first order portal vein thrombosis. Similar studies comparing overall survival for TACE plus Sorafinib versus TACE alone and Sofafinib alone have shown benefit of combination therapy (7-11 months vs 4.9-6.0 months vs 5.9 months). These findings are concordant to the results of this study and highlight the benefit of combination therapy in Child A population with BCLC C disease. 

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Sato Y, Nishiofuku H, Yasumoto T, et al. Multicenter Phase II Clinical Trial of Sorafenib Combined with Transarterial Chemoembolization for Advanced Stage Hepatocellular Carcinomas (Barcelona Clinic Liver Cancer Stage C): STAB Study. J Vasc Interv Radiol 2018; 29:1061-7. 

Post Author:

Anil K Pillai, MD
Associate Professor and Section Chief,
University of Texas Health Science Center
Anil Pillai@AnkupiMD