Pembrolizumab plus lenvatinib with or without hepatic arterial infusion chemotherapy in selected populations of patients with treatment-naive unresectable hepatocellular carcinoma exhibiting PD-L1 staining: a multicenter retrospective study

Background Not all patients with unresectable hepatocellular carcinoma (uHCC) benefit from treatment with immune checkpoint inhibitors and molecular-targeted agents. The aim of this retrospective study was to assess the efficacy and safety of pembrolizumab plus lenvatinib plus hepatic arterial infusion chemotherapy (HAIC) versus pembrolizumab plus lenvatinib in selected populations of patients with treatment-naive uHCC exhibiting programmed cell death ligand-1 (PD-L1) staining. Methods Consecutive patients with treatment-naive uHCC exhibiting PD-L1 staining who were treated with pembrolizumab plus lenvatinib plus HAIC (PLH) or pembrolizumab plus lenvatinib (PL) were retrospectively identified from our medical centres from 2018 to 2021. HAIC involved oxaliplatin, fluorouracil, and leucovorin (FOLFOX). Follow-up occurred every 3 weeks for 1 year and then every 6 weeks thereafter. The primary endpoints included overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the frequency of key adverse events (AEs). Results In total, 248 treatment-naive patients were retrospectively reviewed, 78 of whom were ineligible on the basis of the current criteria. Thus, 170 patients (PLH: n = 84, median age 52 years [range, 42–67]; PL: n = 86, 53 years [range, 43–69]) were eligible for the analysis. The median follow-up was 18.6 months (range, 1–26). At the final follow-up, the median OS was 17.7 months (95% confidence interval [CI], 15.2–18.3) in the PLH group versus 12.6 months (95% CI, 11.1–13.7) in the PL group (hazard ratio [HR] 0.52; 95% CI, 0.36–0.75; p = 0.001). A significant difference was also detected in the median PFS (10.9 months [95% CI, 8.7–11.4] for PLH vs. 6.8 months (95% CI, 5.2–7.4) for PL; HR 0.61, 95% CI, 0.43–0.85; p = 0.001). Significant differences in the rate of the key AEs were noted between groups (79.8% for PLH vs. 62.8% for PL, p = 0.015), but these AEs were controllable. Conclusions Among selected populations of patients with treatment-naive uHCC exhibiting PD-L1 staining, the PLH regimen may substantially improve the survival benefits compared with the PL regimen with a controllable safety profile.