Therapeutic efficacy of lenvatinib in hepatocellular carcinoma patients with portal hypertension

Abstract

Aim Preserved liver function may be an important factor affecting therapeutic efficacy in hepatocellular carcinoma patients treated with lenvatinib, but not all patients can be treated while preserving liver function. This study evaluated the therapeutic efficacy of lenvatinib in patients with poor liver function with and without portal hypertension. Methods This prospectively registered multicenter study analyzed 93 patients treated with lenvatinib. Progression‐free survival was compared between patients with and without advanced portal hypertension according to baseline liver function. Advanced portal hypertension was defined as having both splenomegaly and any portosystemic collaterals. Results A total of 37 patients (40.7%) had advanced portal hypertension. Progression‐free survival did not differ between patients with and without advanced portal hypertension in the entire cohort (median 7.6 vs. 4.1 months, respectively; P = 0.148), but was significantly longer in patients with advanced portal hypertension than in those without advanced portal hypertension in the albumin‐bilirubin grade 2 or 3 group (median 7.6 vs. 2.1 months, respectively; P = 0.016). In a multivariate analysis, the presence of advanced portal hypertension was identified as the only significant predictor associated with prolonged progression‐free survival in the albumin‐bilirubin grade 2 or 3 group. Conclusions Advanced portal hypertension was associated with the therapeutic efficacy of lenvatinib in controlling the progression of hepatocellular carcinoma in patients with poor liver function.

The evolving role of lenvatinib at the new era of first-line hepatocellular carcinoma treatment

“…33,35 In a prospective multicenter study of 93 patients treated with lenvatinib, in which 37 patients had advance portal hypertension, OS did not seem to be compromised by advanced portal hypertension. 36 On the contrary, the risk of variceal bleeding was elevated in IMbrave 150 at 2.4% in the atezolizumab plus bevacizumab group compared to 0.6% in the sorafenib group. Of note, this was a group of well-selected patients benefited from optimal portal hypertension prophylaxis and patients with bleeding esophageal or gastric varices have been excluded from the study already.…”

“…However, bleeding events related to portal hypertension with the use of MTIs (including lenvatinib) were consistently reported to be lower than 2% in the recent published phase 3 trials [ 33 , 35 ]. In a prospective multicenter study of 93 patients treated with lenvatinib, in which 37 patients had advance portal hypertension, OS did not seem to be compromised by advanced portal hypertension [ 36 ]. On the contrary, the risk of variceal bleeding was elevated in IMbrave 150 at 2.4% in the atezolizumab plus bevacizumab group compared to 0.6% in the sorafenib group.…”

Management of Portal Hypertension in Patients with Hepatocellular Carcinoma on Systemic Treatment: Current Evidence and Future Perspectives

“…It is interesting to point out that PH may affect the efficacy of systemic therapy. A prospective multicenter study showed that Lenvatinib prolonged progression-free survival in patients with more severe PH and poorer liver function expressed as albumin-bilirubin score (ALBI) grade 2 or 3, reflecting an increased effect related to changes in drug pharmacokinetics and exposure [76].…”