Identification of prognostic tumor microenvironment in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy in combination with lenvatinib and PD-1 inhibitors.

Abstract

e16141 Background: The triple combination therapy of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC) as a first-line treatment. However, the tumor microenvironment (TME) characteristics of the beneficiary population are still unclear. This study aimed to generally explore the TME characteristics of patients receiving the triple combination therapy by baseline tumor tissues. Methods: A total of 44 patients were prospectively enrolled in this single-center study. Ultimately, 38 biopsy-proven patients were treated with HAIC with oxaliplatin, leucovorin, 5-fluorouracil (FOLFOX), lenvatinib, and PD-1 inhibitors. According to the tumor response elevated by the modified RECIST (mRECIST), the 38 patients were divided into the response group with complete response (CR) and partial response (PR) and the non-response group with stable disease (SD) and progression disease (PD). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Meanwhile, the cancer gene-targeted next-generation sequencing (NGS) and RNA sequencing (RNA-seq) were performed to describe the differences between the two groups of biopsy samples to identify the prognostic TME characteristics. Results: Among the 38 patients, 22 patients were distributed to the response group, and the remaining 16 patients were included in the non-response group. The response group and the non-response group were significantly different in median OS (not-reached vs. 8.6 months; HR, 0.22, 95% CI 0.08-0.58; p< 0.001) and median PFS (15.3 months vs. 2.0 months; HR, 0.31, 95% CI 0.13-0.75; p= 0.001). The most common AEs were AST elevation (84.2%), stomachache (76.3%), nausea (63.2%), and hypertension (52.6%). Grade 3/4 AEs occurred 14 times among 12 patients, and no treated-related deaths were observed. For the cancer gene-targeted NGS, no specific enrichment for gene mutations was identified to be related to prognosis. As for the TME analysis by RNA-seq, the response group was characterized by a more beneficial infiltration of immune cell subsets, and high tumor-infiltrating T lymphocytes were associated with a higher response rate, longer PFS and OS. Conclusions: In this study, HAIC plus lenvatinib and PD-1 inhibitor as first-line therapy displayed promising efficacy and manageable side effects in patients with advanced HCC. The differences in the initial TME of patients, especially in tumor-infiltrating T lymphocytes, may be potential biomarkers for predicting response and prognosis. This finding provides clues to search for biomarkers for the triple combination therapy of HAIC combined with lenvatinib and PD-1 inhibitors in advanced HCC.