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

Abstract

Aims 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). Methods A total of 61 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 and overall survival 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 grade (hazard ratio 0.372, 95% CI 0.157–0.887; p = 0.0241) and tumor morphology (hazard ratio 0.322, 95% CI 0.116–0.889; p = 0.0287) were independently associated with progression‐free survival in patients with tm50%LO HCC. In VP4 HCC, median progression‐free survival was worse in CP‐B (57 days) than in CP‐A patients (137 days, p = 0.0462). Conclusions 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.

Comprehensive Treatment of Trans-Arterial Chemoembolization Plus Lenvatinib Followed by Camrelizumab for Advanced Hepatocellular Carcinoma Patients

“…Lenvatinib has been approved for first-line treatment of patients with unresectable advanced HCC in many countries. The safety and efficacy of lenvatinib for HCC patients has been demonstrated in clinical practice in many studies ( Chuma et al, 2020 ; Han et al, 2020 ). Since 2018, lenvatinib has become another first-line systemic treatment for HCC patients and is deemed an alternative to sorafenib due to its comparable efficacy ( Kudo et al, 2018 ).…”

Early response and safety of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in patients who do not meet IMbrave150 eligibility criteria

“…In the REFLECT trial, the multikinase inhibitor lenvatinib 9 was not inferior to sorafenib with respect to OS. The results of these clinical trials have been confirmed in numerous real‐world studies 10–14 …”

Treatment strategies for hepatocellular carcinoma with extrahepatic metastasis

“…Notably, the REFLECT trial excluded patients with adverse prognostic tumor characteristics, such as main branch portal vein thrombosis or greater than 50% tumor occupation of the liver, which are commonly seen in advanced stage and nearly unavoidable in routine clinical decision making. Recent studies have found that Lenvatinib also offered a survival benefit in patients with highly advanced HCC and may lead to more favorable outcomes compared with Sorafenib[ 16 - 18 ]. Approval for Lenvatinib was granted by the Food and Drug Administration (FDA) as the first-line agent, and it was included in the latest BCLC and EASL guidelines[ 1 , 3 ].…”