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Research progress regarding programmed cell death 1/programmed cell death ligand 1 inhibitors combined with targeted therapy for treating hepatocellular carcinoma

ABSTRACT: In recent years, a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma (HCC), including sorafenib, lenvatinib, and regorafenib. Immunotherapy is considered to be an effective treatment for advanced HCC. Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC. However, treating advanced HCC is still a great challenge, and the need for new treatments remains urgent. This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.

SUBMITTER: Zheng L

PROVIDER: S-EPMC8554719 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionProgrammed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling blockade is the most effective strategy for the treatment of immune evading hepatocellular carcinoma (HCC). While immune checkpoint inhibitor has revolutionized the concept of cancer treatment, it has also led to unexpected tumor growth. Regulatory T cells express PD-1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) receptors, which are proliferated and activated by antibody binding, and their ratio to CD8+ T cells is altered, which is one of the causes for hyper progressive disease (HPD). We examined the frequency of HPD in anti-PD-1/PD-L1 monotherapy and combination therapy with vascular endothelial growth factor (VEGF) antibody and anti-CTLA-4 antibodies.MethodsThis was a prospective and retrospective cohort study which enrolled 198 patients with unresectable HCC from January 2015 to December 2021 at the Kindai University Hospital. Fifty-eight patients received anti-PD-1/PD-L1 monotherapy, 119 patients combination with VEGF antibody, and 21 patients combination with anti-CTLA-4 antibody. We defined HPD as tumor growth rate (TGR) ratio ≥4, ΔTGR ≥40%, and tumor growth kinetics ratio ≥4.ResultsThe HPD rate was 10.3% (6/58) in anti-PD-1/PD-L1 monotherapy, 1.7% (2/119) in combination with VEGF antibody, and 4.8% (1/21) in combination with anti-CTLA-4 antibody (p = 0.034). The odds ratio for HPD in the combined anti-CTLA-4 antibody group was 0.433 (95% confidence interval [CI]: 0.05-3.83) when compared to the anti-PD-1/PD-L1 monotherapy group and 2.93 (95% CI: 0.25-33.79) when compared to the combined VEGF antibody group.ConclusionThe frequency of HPD in unresectable HCC compared to anti-PD-1/PD-L1 monotherapy was decreased with the combination with anti-VEGF antibody and not increased with anti-CTLA-4 antibody. Anti-PD-1/PD-L1 combined with anti-CTLA-4 antibody is now available in real-world and needs to be further validated with accumulated clinical practice.

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Research progress regarding programmed cell death 1/programmed cell death ligand 1 inhibitors combined with targeted therapy for treating hepatocellular carcinoma

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