Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma

Abstract

The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child–Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin–bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.

The action and resistance mechanisms of Lenvatinib in liver cancer

“…However, Lenvatinib showed an insignificant OS improvement compared to Sorafenib with 13.6 months compared to 12.3 months, respectively 14 . However, it should be noted in a subsequent phase II trial where Lenvatinib dosage was increased, the median OS was 18.7 months 17 and in yet another study OS increased to 20.2 months 18 . While the improved ORR and PFS are important, increasing the OS time is the most crucial aspect of proving noninferior that Lenvatinib fell short on.…”

“…These results have strong implications that Pembrolizumab in combination with Lenvatinib not only allows for synergistic properties in slowing the progression of the cancer but also has an anti‐resistant property if patients are able to continue treatment for longer. Lastly, the median OS was 22 months 69 compared to 14−20.2 months 14,17,18 depending on dosage with Lenvatinib alone. The improvement in OS also supports the conclusion that ICIs such as Pembrolizumab may slow cancer in becoming resistant to Lenvatinib.…”

“…14 However, it should be noted in a subsequent phase II trial where Lenvatinib dosage was increased, the median OS was 18.7 months 17 and in yet another study OS increased to 20.2 months. 18 While the improved ORR and PFS are important, increasing the OS time is the most crucial aspect of proving noninferior that Lenvatinib fell short on. This may partly be due to Lenvatinib resistance acquired by patients.…”

Effectiveness and safety of lenvatinib plus anti‐programmed death‐1 antibodies in patients with hepatocellular carcinoma: A real‐world cohort study

“…Based on either Child‐Pugh class or albumin–bilirubin (ALBI) score, impaired liver function has been associated with poor OS in previous trials, whether evaluating targeted therapies or ICBs. 15 , 16 , 17 There is an outstanding need for a large dataset evaluating treatment outcomes and toxicity profiles in real‐world patients, including those with poor liver function, especially when treated with combinations of targeted therapies and ICBs. Here, we report the real‐world data on the efficacy and safety of lenvatinib plus anti‐PD‐1 antibodies in a retrospective cohort of patients with unresectable or advanced HCC.…”

“…In real‐world practice, patients receiving combination therapy often suffer from poor liver function, due to the high tumor load and/or adverse effects of prior treatment. Based on either Child‐Pugh class or albumin–bilirubin (ALBI) score, impaired liver function has been associated with poor OS in previous trials, whether evaluating targeted therapies or ICBs 15–17 . There is an outstanding need for a large dataset evaluating treatment outcomes and toxicity profiles in real‐world patients, including those with poor liver function, especially when treated with combinations of targeted therapies and ICBs.…”