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

Abstract

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.

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

“…All of the included studies came from China, and all the studies were retrospective, three of which were multi-centered ( 25 , 30 , 34 ). The baseline characteristics in each study were depicted in Table 1 , as well as the results of quality assessment.…”

“…PFS at 0.5, 1, 1.5, and 2 years were evaluated in 13 ( 21 , 25 , 31 – 38 , 40 – 42 ), 13 ( 21 , 25 , 31 – 38 , 40 – 42 ), 11 ( 21 , 25 , 31 – 37 , 41 , 42 ), and 5 studies ( 21 , 32 , 34 , 37 , 42 ), and the pooled rates and 95%CI were 0.781 (0.688-0.862), 0.387 (0.293-0.486), 0.117 (0.076-0.165), and 0.069 (0.005-0.182), respectively ( Table 3 ). OS at 0.5, 1, 1.5, 2, and 3 years were evaluated in 12 ( 21 , 25 , 31 – 36 , 39 – 42 ), 12 ( 21 , 31 – 34 , 39 – 42 ), 12 ( 21 , 31 – 34 , 39 – 42 ), 9 ( 21 , 31 – 34 , 39 – 42 ), and 5 studies ( 21 , 31 – 33 , 42 ), and the pooled rates and 95%CI were 0.943 (0.902-0.975), 0.690 (0.585-0.786), 0.385 (0.246-0.533), 0.212 (0.117-0.324), and 0.056 (0.028-0.091), respectively ( Table 3 ).…”

“…TACE was adopted in 10 studies ( 21 , 30 – 33 , 38 – 42 ), and HAIC were in 5 studies ( 25 , 34 – 37 ), respectively. Table 4 exhibited the outcomes using TACE+TKIs+ICIs and HAIC+TKIs+ICIs, respectively.…”

“…There were 7 studies incorporating the control group ( 21 , 25 , 33 – 35 , 39 , 40 ), and the control group was TACE+TKIs in three studies ( 21 , 33 , 40 ), TKIs+ICIs in three ( 34 , 35 , 39 ), and TKIs in one ( 25 ), respectively. Results showed that TACE/HAIC+TKIs+ICIs was superior to TKIs alone in all fields ( Table 5 ), and similar advantage were also observed compared to TACE+TKIs and TKIs+ICIs (all P<0.05, Table 5 ).…”

Long term complete response of advanced hepatocellular carcinoma to glypican-3 specific chimeric antigen receptor T-Cells plus sorafenib, a case report

“…The approval of atezolizumab plus bevacizumab suggests that immunotherapy combined with other medication is an effective therapeutic strategy to achieve a b e t t e r c l i n i c a l r e s p o n s e . T h e c o m b i n a t i o n o f immunotherapeutic agents with other medications, including tyrosine kinase inhibitors, has also been demonstrated to be effective as first-line in patients with metastatic HCC but the combination with immune cell therapy is rarely reported (4)(5)(6). Chimeric antigen receptor (CAR) T-cell therapy has achieved outstanding efficacy in hematological malignancies and shown potential anti-tumor efficacy in early phase clinical trials for the treatments of solid tumors including advanced HCC (aHCC) (7,8).…”