Analysis of efficacy of lenvatinib treatment in highly advanced hepatocellular carcinoma with tumor thrombus in the main trunk of the portal vein or tumor with more than 50% liver occupation: a multicenter analysis.

PURPOSE To assess the safety, efficacy and prognostic impact of clinical factors associated with lenvatinib treatment in highly advanced hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein trunk (VP4) or tumor with more than 50% liver occupation (tm50%LO). METHOD Sixty-one highly advanced HCC patients (41 patients with tm50%LO and 20 patients with VP4) who were treated with lenvatinib at multicenter were enrolled and retrospectively analyzed for treatment outcomes according to their clinical status, including tumor morphology. RESULTS The most frequent ≥ grade 3 adverse event in tm50%LO HCC was elevated aspartate aminotransferase (17.1%). Objective response rates were 37.5% and 0% in tm50%LO HCC patients with Child-Pugh grade (CP)-A and CP-B, respectively and 26.7% and 0% in VP4 HCC patients with CP-A and CP-B, respectively. Estimated median progression free survival (PFS) and overall survival (OS) were 132 days and 229 days, and 101 days and 201 days in patients with tm50%LO and VP4, respectively. In multivariate analysis, modified albumin-bilirubin (mALBI) grade (hazard ratio (HR), 0.372; 95%CI, 0.157-0.887; P=0.0241) and tumor morphology (HR, 0.322; 95%CI, 0.116-0.889; P=0.0287) were independently associated with PFS in patients with tm50%LO HCC. In VP4 HCC, median PFS was worse in CP-B (57 days) than in CP-A patients (137 days, P=0.0462). CONCLUSION Lenvatinib treatment offers a benefit in highly advanced HCC (tm50%LO or VP4) patients with good liver function or nodular type tumor. The various characteristics identified in this study might be useful as indicators of lenvatinib treatment in highly advanced HCC with tm50%LO or VP4, which are considered very refractory cancers.