Sorafenib plus intra-arterial cisplatin versus sorafenib alone in patients with advanced hepatocellular carcinoma: A randomized phase II trial.

4076 Background: Intra-arterial cisplatin therapy for advanced hepatocellular carcinoma (HCC) has been reported a favorable tumor-shrinking effect and long-term survivals even in pts with highly advanced HCC. The aim of this trial was to evaluate the efficacy and safety ofsorafenib plus intra-arterial cisplatin (SP) vs. sorafenib alone (S) for advanced HCC. Methods: In this multicenter open-labeled randomized phase II trial, advanced HCC pts with no prior chemotherapy and Child Pugh A or B7 were randomly assigned 2:1 to receive SP (sorafenib: 800 mg, twice daily; intra-arterial cisplatin: 65 mg/m2, day 1, every 4 to 6 weeks up to a maximum of 6 cycles) or S (800 mg, twice daily) with portal vein tumor thrombosis and extrahepatic metastasis as dynamic allocation factors. The primary endpoint was overall survival. If the median survival of S is assumed as 7.0 months and that of SP as 9.5 months, the hazard ratio (HR) is 0.74. SP would be judged as favorable if HR is 0.74 or lower. A total of 105 pts was needed to estimate the 1-year survival rate with an accuracy of ±10%. Results: From June 2011 to December 2013, 108 pts were randomized (SP, n = 66; S, n = 42) and followed up to December 2014. In the full analysis set of 106 pts, the patient characteristics were well-balanced, except for portal vein tumor thrombosis and hepatitis C viral infection. The median survivals in the SP and the S arms were 10.6 and 8.7 months, respectively (crude HR [95% CI], 0.68 [0.44-1.04], p = 0.073; and stratified HR by the allocation factors [95% CI], 0.60 [0.38-0.96], p = 0.031). The median time to progression was 3.1 and 2.8 months in the SP and S arms (HR [95% CI], 0.78 [0.52-1.16], p = 0.212; stratified HR [95% CI], 0.78 [0.59-1.21]). The following adverse events were more frequent in the SP arm than in the S arm, (percentage in the SP/S arms): neutropenia, 60.0/43.9; leukocytopenia, 75.4/43.9; hemoglobin, 89.2/73.2; thrombocytopenia, 89.2/80.5; hyponatremia, 81.5/53.7; nausea, 41.4/19.5; and hiccups, 9.2/0.0, respectively. Conclusions: According to the prespecified HR of 0.74, SP yielded favorable overall survival as compared to S in pts with advanced HCC. A further phase III trial is warranted to confirm these results. Clinical trial information: UMIN000005703.