Efficacy and Safety of Lenvatinib for Advanced Hepatocellular Carcinoma Patients Beyond REFLECT Study Indications in a Real-World Setting in China

Abstract Background/purpose: Lenvatinib was found to be non-inferior to sorafenib in a Phase 3 REFLECT trial on advanced hepatocellular carcinoma. However, patients with a liver tumor volume of greater than 50% of total liver volume or with main portal vein tumor thrombus, which often occurs in clinical practice, were excluded from the REFLECT trial. This study aimed to examine the safety and efficacy of lenvatinib on patients beyond REFLECT study indications in a real-world setting.Method: This was a retrospective, single-center observational study focused on unresectable hepatocellular carcinoma (u-HCC) patients with the tumor accounting for more than 50% of the liver volume or with main portal vein tumor thrombus. From June 2018 to February 2019, 21 u-HCC patients with above characteristics were enrolled. The therapeutic effects were determined using the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) in the 12th week. Grades of adverse events followed with the Common Terminology Criteria for Adverse Events version (CTCAE) 4.0. The median Progression-Free Survival (PFS) and median Over Survival (OS) were determined at the 12th month.Results: The median observation period was 11.5 months. Fatigue, leukopenia and dysphoria were the most frequent adverse events. Leukopenia, hand-foot skin reaction and decreased appetite were the most frequent adverse events, and were higher than Grade 2. 7 of the patients had elevated Child-Pugh scores, 3 of whom increased from Child-Pugh A to B. All of the adverse events could be controlled by appropriate dose reduction, interruption and symptomatic treatment. No liver function failure occurred. The probability of tumor marker (AFP or PIVKA-II) decline was 100% and 60% at one month and three months after administration respectively. In the m-RECIST evaluation in the 12th week, 0, 7, 7 and 7 patients achieved complete response, partial response, stable disease and progressive disease respectively. The objective response rate was 33.3%. The median PFS and OS was 5.3 and 11.2 , respectively. 1 year survival rate was 42.9%.Conclusion: Lenvatinib treatment can be accomplished with safety and a good response for patients beyond REFLECT study indications in a real-world setting.