Efficacy and safety of anti-PD-1 monoclonal antibody combined with sorafenib or lenvatinib in treatment of patients with Child-Pugh class B unresectable hepatocellular carcinoma / 临床肝胆病杂志

ABSTRACT

ObjectiveTo investigate the safety and efficacy of tyrosine kinase inhibitors combined with immune checkpoint inhibitors in the treatment of patients with Child-Pugh class B unresectable hepatocellular carcinoma （uHCC）. MethodsA total of 96 patients with Child-Pugh class B uHCC who were admitted to Beijing Ditan Hospital， Capital Medical University， from December 31， 2020 to March 30， 2023 were enrolled as subjects， among whom 63 patients receiving lenvatinib combined with programmed death-1 （PD-1） inhibitor were enrolled as L group and 33 patients receiving sorafenib combined with PD-1inhibitor were enrolled as S group. The primary endpoint was objective response rate （ORR）， and secondary endpoints included time to progression （TTP）， overall survival （OS）， toxicity， drug withdrawal rate， and dose adjustment rate. The The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Survival curves were plotted， and the Kaplan-Meier method was used to calculate the survival rate of patients in both groups， while the Log-rank test was used for comparison between the two groups. The Cox regression model was used to calculate hazard ratio （HR） and its 95% confidence interval （CI） and perform the multivariate analysis of influencing factors for prognosis. ResultsAmong the 96 patients with uHCC， 55 （57.3%） had Child-Pugh class B （7 points） uHCC and 41 （42.7%） had Child-Pugh class B （8—9 points） uHCC. The L group had a significantly higher ORR than the S group （46.0% vs 15.2%， P=0.003）， and there were no significant differences between the L group and the S group in median TTP （6.6 months vs 3.5 months， P=0.48） or OS （13.8 months vs 13.2 months， P=0.95）. There was no significant difference in median TTP between the patients with Child-Pugh class B （7 points） uHCC and those with Child-Pugh class B （8—9 points） uHCC （6.6 months vs 4.8 months， P=0.35）， while there was a significant difference in OS between these two groups of patients （14.5 months vs 8.8 months， P=0.045）. The multivariate analysis showed that ORR was a protective factor for both TTP （HR=0.18， 95%CI： 0.09 ‍—‍ 0.36， P<0.001） and OS （HR=0.20， 95%CI： 0.09 ‍—‍ 0.43， P<0.001）. There were no significant differences between the L group and the S group in the overall incidence rate of adverse reactions （98.4% vs 97.0%） and the incidence rate of grade≥3 adverse reactions （68.3% vs 63.6%）， and there were also no significant differences between the two groups in dose adjustment rate （84.8% vs 70.2%） and drug withdrawal rate （56.1% vs 72.7%）. ConclusionCompared with the regimen of sorafenib combined with PD-1 inhibitor， the regimen of lenvatinib combined with PD-1 inhibitor can improve the ORR of patients with Child-Pugh class B uHCC， with similar prognosis and safety profile between the two groups.