Lenvatinib plus checkpoint inhibitors (ICIs) versus sorafenib plus ICIs as first-line treatment for unresectable hepatocellular carcinoma with Child-Pugh B

The efficacy and safety of tyrosine kinase inhibitors combined with check-point inhibitors (ICIs) in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh B had not been evaluated.

In this single-center, prospective cohort study, patients with previously untreated unresectable HCC (uHCC) with Child-Pugh B were enrolled. They were divided into two groups: one for Lenvatinib plus check-point inhibitors [ICIs] (Arm L; orally once daily, 8 mg for body weight ≥60 kg or 4 mg for body weight < 60 kg as the initial doses) and another for sorafenib plus ICIs (Arm S; 200 mg orally twice daily as the initial dose in 28-day cycles). The primary endpoint was time-to-progression (PFS; time free survival) and secondary endpoints included objective response rate (ORR), toxicity, drug discontinuation and dose reduction. Prognostic factors were evaluated using a multivariable Cox proportional hazards model.

Between May 30, 2020 and December 31, 2022, 90 patients were included (Arm L, n=57; Arm S, n=33). With a median follow-up time of 15.9 months, the median age of patients was 63 (range, 29-82) years and most of them (86.7%) were male. Among them, 82 cases (91.1%) had hepatitis-B virus infection. 55 patients (61.1%) had type I-IV portal vein tumor thrombosis and 24.4% (22) of the cohort presented with lung metastasis. Patients with Child-Pugh B7 accounted for 55.4% (50) and the ratio of patients with B8/9 was 44.6% (40). 67 patients had performed transcatheter arterial chemoembolization (TACE). Patients in Arm L had a significantly higher ORR (43.9% vs 18.2%, P=0.021). But no difference had been demonstrated in median PFS (6.6 vs 3.5 months, P=0.67) or OS (12.4 vs 13.8 months, P=0.92) between Arm L and Arm S. Neither no significant difference in mPFS or mOS had been found between patient with Child-Pugh B7 and those with Child-Pugh B8/9. Patients who received systemic therapy combined with cTACE showed significantly improved median PFS (6.6 vs 2.8 months, P < 0.001) and OS (13.9 vs 8.0 months, P=0.011). Multivariable analysis showed that tumor objective response was identified as the significant favorable factor for both PFS (HR 0.19, 95%CI 0.098-0.38, P < 0.001) and OS (HR 0.20, 95%CI 0.087-0.44, P < 0.001). Also, the combination of TACE was significantly associated with longer PFS (HR: 0.55 [95% CI: 0.30-1.0]; P=0.05). Comparable safety profiles were observed in Arm L and S. No significant difference in dose reductions (84.8% vs 70.2%) or drug discontinuations (56.1% vs 72.7%) was reported between Arm L and Arm S.

The regimen of Lenvatinib plus ICIs had improved ORR compared to the regimen of sorafenib plus ICIs for uHCC with Child-Pugh B. After treating with sorafenib plus ICIs or Lenvatinib plus ICIs, the prognosis of patients with uHCC was similar between the subgroup of those with Child-Pugh B7 and those with Child-Pugh B8/9.

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The authors.

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All authors have declared no conflicts of interest.