CDX-2 expression correlates with clinical outcomes in MSI-H metastatic colorectal cancer patients receiving immune checkpoint inhibitors

Abstract

Abstract Background Immune checkpoint inhibitors (ICIs) showed efficacy in metastatic colorectal cancer (mCRC) with mismatch-repair deficiency or high microsatellite instability (dMMR-MSI-H). Unfortunately, a patient’s subgroup did not benefit from immunotherapy. CDX-2 would seem to influence immunotherapy’s sensitivity, potentially being a biomarker of ICIs efficacy. Therefore, we investigated its role as a prognostic-predictive marker in patients with mCRC MSI-H. Materials and Methods We retrospectively collected data from 14 MSI-H mCRC patients treated with ICIs between 2018 and 2021. The primary endpoint was the Progression-Free-Survival (PFS) rate at 12 months. The secondary endpoints were Overall Survival (OS), PFS, objective response rate (ORR), and disease control rate (DCR). Results The PFS rate at 12 months was 80% in CDX-2-positive patients vs 0% in CDX-2-negative patients (p = 0.003). The median PFS was not reached (NR) in the CDX-2-positive group versus 2.07 months (95%CI 2.07to10.8) in CDX-2-negative patients (p = 0.0003). Median OS was NR in CDX-2-positive patients versus 2.17 months (95%CI 2.17to18.7) in CDX2-negative patients (p = 0.0262). All CDX-2-positive patients achieved a disease response, one of them a complete response. Among CDX-2-negative patients, one achieved stable disease, while the other progressed rapidly (ORR:100%v0%, p = 0.0005; DCR: 100%vs50%, p = 0.02). Pembrolizumab in the first-line did not reach the median PFS, and it achieved a median PFS of 10.8 months (95%CI 10,8to12,1; p = 0.04) in third-line treatment. Conclusion Our analysis confirms the prognostic role of CDX-2 in CRC and suggests a promising predictive role in defining the immuno-sensitive population. Modulating the CDX-2/CXCL14 axis in CDX-2-negative patients could be useful in overcoming primary resistance to immunotherapy.