Impact of Immune Checkpoint Inhibitors with or without a Combination of Tyrosine Kinase Inhibitors on Organ-Specific Efficacy and Macrovascular Invasion in Advanced Hepatocellular Carcinoma

Abstract

Introduction: The tumor microenvironments of different organs often differ and thus may affect the immunotherapy response. Objective: This study elucidated that the efficacy of programmed cell death protein-1 (PD-1) inhibitors varies across different metastatic sites among individuals with advanced hepatocellular carcinoma (HCC). Methods: We retrospectively analyzed treatment outcomes in advanced HCC patients receiving PD-1 inhibitors with or without a combination of tyrosine kinase inhibitors (TKIs). Both the overall response rate (ORR) and organ-specific response rate (OSRR) were assessed using Response Evaluation Criteria in Solid Tumors 1.1 criteria. A survival analysis and its predictors were determined using a multivariate analysis. Results: We analyzed 42 advanced HCC patients (median age: 58.0 years; 78.6% males). Thirty (71.4%) patients were sorafenib-experi-Hsin-Yu Kuo and Nai-Jung Chiang are co-first authors. Hong-Ming Tsai and Yih-Jyh Lin contributed equally to this work.

Real-world outcome of immune checkpoint inhibitors for advanced hepatocellular carcinoma with macrovascular tumor thrombosis

“…Our findings are in agreement with a report which addressed a complete response of IVCT to ICIs in advanced-stage renal cell carcinoma and proposed the response of vascular thrombi to ICIs being stronger in a high T-cell inflamed tumor microenvironment [22]. These findings indicate that ICIs markedly decrease or stabilize tumor thrombus volume, and this response may be affected by the diversity of tumor microenvironments [13,14,23]. In addition, the regression of vascular metastases may preserve organ function and prevent distant metastasis, thus offering further curative treatment either alone or in combination with other modalities for non-responding organs.…”

“…To assess the vascular response, the largest diameters of the tumor thrombus were measured and compared with the basal value recorded [ 21 ] and categorized as follows: complete remission (CR), i.e., complete disappearance of the tumor thrombus; partial response (PR), i.e., at least a 30% decrease in thrombus diameters; stable disease (SD), i.e., a decrease of < 30% or an increase of < 20%; and progressive disease (PD), i.e., an increase of ≥ 20% in the sum of the diameters [ 13 ]. Objective response rate of tumor thrombi (ORRT) was defined as the total number of patients achieving CR or PR, and disease control rate of tumor thrombi (DCRT) was defined as the total number of patients achieving CR, PR, or SD.…”

“…Despite these promising results, concrete data regarding ICI treatment for advanced HCC patients with MVI in clinical settings are still rare [13][14][15]. Additionally, there have been no randomized clinical trials yet to assess the treatment outcomes with regard to these patients.…”

Organ Specific Responses to First-line Lenvatinib Plus Anti-PD-1 Antibodies in Patients With Unresectable Hepatocellular Carcinoma: a Retrospective Analysis

“…In support of the latter explanation, recent clinical trials in advanced HCC have shown a trend for higher ORRs overall with combined TKI and anti-PD-1 antibody therapy (13,25) versus anti-PD-1 antibody monotherapy (26) or dual immune-therapy strategies. (27,28) Finally, in the present study, the OSRR for lung metastases was similar to previous reports of immune checkpoint inhibitor monotherapy (37 vs. 40% (16) and 41.2% (17)). However, due to the small number of patients with lung metastasis included in the present study, the conclusions that can be drawn are limited.…”

“…There have been previous reports of organ-speci c responses to immunotherapy in the second-line treatment of HCC. (16,17) However, to our knowledge, this is the rst report of organ-speci c responses to rst-line combination treatment with lenvatinib plus anti-PD-1 antibodies in patients with advanced HCC.…”