ABCA1 and ABCG1 cholesterol transporters expression on metastatic renal cell carcinoma: Impact on immunotherapy outcomes (CHOMET study).

Abstract

568 Background: Although immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, most patients do not achieve benefits, emphasizing the need to understand the mechanisms of resistance. Previous analysis highlighted the association between blood cholesterol levels, passive cholesterol diffusion efflux and oncological outcomes. Here we reported the preliminary data of the CHOMET study, aimed at assessing the cholesterol transporters ABCA1 and ABCG1 expression in ICIs-treated patients with metastatic renal cell carcinoma (mRCC). Methods: The present is a monocentric retrospective study on patients with mRCC receiving first-line ICI-based combination. The primary objective was to assess the ABCA1/G1 expression by immunohistochemistry and its impact on overall survival (OS). The secondary objectives included the impact on progression-free survival (PFS) and disease control rate (DCR: complete and partial responses plus stable disease). Survival times were calculated by Kaplan-Meier method and comparisons between groups were performed by log-rank test. Results: 61 patients were enrolled, clear cell RCC was the most frequent histotype (78.8%). With a median follow-up of 30.4 months (22.1-37.0), median OS was 38.9 months (CI 33.9-NR) and median PFS was 24.4 months (CI 10.1-34.2). For the present analysis, the ABCA1/G1 histological evaluation of tumour samples was available for 43 and 41 patients, respectively. The median expression level was 50% for ABCA1 and 45% for ABCG1. We found a significant correlation between higher ABCA1/G1 staining intensity expression and both shorter median OS and PFS (Table). Similarly they were inversely related to DCR (Table). Conclusions: For the first time, we reported a high expression of ABCA1/G1 cholesterol transporter on kidney cancer. An inverse association between staining intensity expression and oncological outcomes in patients receiving ICIs combinations was found. Oncological outcomes according to ABCA1/G1 staining intensity expression. IHC mPFS months (95%CI) mOSmonths (95%CI) DCR% ABCA1 intensity expression 1+ 30.1 (25.8-NR) NR (NR-NR) 88.9 2+ 24.4 (9.9-NR) NR (33.9-NR) 72.7 3+ 4.5 (3.20-NR) 12.2 (8.2-NR) 25.0 p value 0.016 < 0.001 0.013 ABCG1 intensity expression 1+ 62.7 (25.6-NR) NR (NR-NR) 87.5 2+ 17.4 (9.9-NR) NR (NR-NR) 68.2 3+ 6.65 (2.9-NR) 12.2 (3.8-NR) 37.5 p value 0.006 0.013 0.101 DCR: disease control rate, IHC: immunohistochemistry, mOS: median overall survival, mPFS: median progression-free survival, NR: not reached.