Real-world efficacy and prognostic factors of lenvatinib plus PD-1 inhibitors in 378 unresectable hepatocellular carcinoma patients

Abstract

Introduction Combining lenvatinib with a programmed cell death protein-1 (PD-1) inhibitor has been explored for the treatment of un-resectable hepatocellular carcinoma (uHCC). This study aimed to investigate the real-world efficacy of and prognostic factors for survival associated with lenvatinib plus PD-1 inhibitor treatment in a large cohort of Asian uHCC patients even the global LEAP-002 study failed to achieve the primary endpoints. Methods Patients with uHCC treated with lenvatinib and PD-1 inhibitors were included. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR) and adverse events (AEs). Prognostic factors for survival were also analyzed. Results A total of 378 uHCC patients from two medical centers in China were assessed retrospectively. The median patient age was 55 years, and 86.5% of patients were male. Hepatitis B virus (HBV) infection (89.9%) was the dominant etiology of uHCC. The median OS was 17.8 (95% confidence interval (CI) 14.0–21.6) months. The median PFS was 6.9 (95% CI 6.0–7.9) months. The best ORR and disease control rate (DCR) were 19.6% and 73.5%, respectively. In multivariate analysis, Child‒Pugh grade, Barcelona Clinic Liver Cancer stage, Eastern Cooperative Oncology Group performance status score, involved organs, tumor burden score, and combination with local therapy were independent prognostic factors for OS. A total of 100% and 57.9% of patients experienced all-grade and grade 3/4 treatment-emergent AEs, respectively. Conclusion This real-world study of lenvatinib plus PD-1 inhibitor treatment demonstrated long survival and considerable ORRs and DCRs in uHCC patients in China. The tolerability of combination therapy was acceptable but must be monitored closely.

Lenvatinib applicability in the therapeutic strategy of patients with hepatocellular carcinoma

“…Further, lenvatinib monotherapy seemed to be stronger than the other control arms with sorafenib in terms of OS (19.0 months for lenvatinib vs. 13.4–15.5 months for sorafenib) as well as ORR (17.5% for lenvatinib vs. 5.1–11% for sorafenib). These encouraging data of the combination of lenvatinib plus PD-1 inhibitors were found as well in real-world setting of a HCC Chinese population harboring a heterogeneity in general status (ECOG PS 0 to 2) and liver functions (Child-Pugh A and B) ( 16 ). Globally, OS was 17.8 months (95% CI: 14.0–21.6) with ORR at 19.6% (95% CI: 15.6–23.6%).…”

“…In real-world setting from a Chinese population of 378 patients treated by lenvatinib plus PD-1 inhibitors, data were quite similar, showing 57.9% TRAE of grade 3–4, but higher rate of treatment discontinuation (24.6%). The most frequent grade 3–4 TRAEs were arterial hypertension (15.1%), increased blood bilirubin levels (8.5%), fatigue (7.7%), proteinuria (7.1%), decreased platelet count (6.9%), decreased appetite (6.3%), hypokalemia (6.3%), and diarrhea (5.8%) ( 16 ).…”

Hepatic arterial infusion chemotherapy combined with lenvatinib and PD‐1 inhibitors versus lenvatinib and PD‐1 inhibitors for HCC refractory to TACE

“…Lenvatinib-based combination therapy is the most common selection, which has been proved to provide inspiring tumor control and survival benefits for unresectable or advanced HCC. 27,28 Considering the increased applications of hepatic arterial chemotherapy (HAIC) in advanced HCC, this study aimed to investigate the efficacy and safety of HAIC added to the Lenvatinib-ICIs therapy, anticipating achieving superior oncological outcomes. For unresectable HCC, the combination of lenvatinib and pembrolizumab achieved an ORR of 46.0% in a Phase IB study.…”

“…Although the current guidelines recommend “A + T” or durvalumab plus tremelimumab (D + T) as first‐line systemic therapies for TACE‐refractory or advanced HCC, only a small proportion of patients in our clinical practice choose the above regimens mainly due to financial burdens. Lenvatinib‐based combination therapy is the most common selection, which has been proved to provide inspiring tumor control and survival benefits for unresectable or advanced HCC 27,28 . Considering the increased applications of hepatic arterial chemotherapy (HAIC) in advanced HCC, this study aimed to investigate the efficacy and safety of HAIC added to the Lenvatinib‐ICIs therapy, anticipating achieving superior oncological outcomes.…”

Efficacy and safety of different PD-1 inhibitors in combination with lenvatinib in the treatment of unresectable primary liver cancer: a multicentre retrospective study

“…The phase III LEAP-002 study, which compared the combination of lenvatinib and pembrolizumab with the combination of lenvatinib and placebo as first-line treatment for advanced unresectable hepatocellular carcinoma, did not meet the primary endpoints of overall survival (OS) and progression-free survival (PFS) [ 17 ]. A result from a large-scale real-world study showed that there was no significant difference in OS between the combination of lenvatinib and pembrolizumab and the combination of lenvatinib with other programmed cell death protein 1 (PD-1) inhibitors [ 18 ].…”