RNA Expression-Based Analysis to Predict Response in Patients with Metastatic Mismatch Repair Proficient Colorectal Cancer Treated with Regorafenib and Nivolumab.
Academic Article
Overview
abstract
INTRODUCTION: We previously conducted a phase I/Ib study (NCT03712943) with regorafenib and nivolumab in patients with refractory metastatic mismatch repair proficient (pMMR) colorectal cancer (CRC). This study aimed to investigate the role of Xerna™ TME Panel in predicting the treatment response. METHODS: Twenty-two archival pretreatment tumor samples were subjected to the Xerna™ TME Panel, a machine learning-based RNA-sequencing biomarker assay. The Xerna tumor microenvironment (TME) subtypes were evaluated for correlation with overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and other biomarkers including KRAS, PD-L1, CD8 expression, and Treg cells in TME. RESULTS: Based on Xerna™ TME Panel, 4 patients with immune-active (IA) subtype and 6 patients with immune-suppressed subtype were classified as biomarker-positive, and five with angiogenic (A) subtype and seven with immune desert subtype were biomarker-negative. While not reaching statistical significance, Xerna TME biomarker-positive patients seemed to have longer median PFS (7.9 vs. 4.1 months, p = 0.254), median OS (15.75 vs. 11.9 months, p = 0.378), and higher DCR (70% vs. 58%, p = 0.675). The IA subtype in our cohort had higher levels of CD4+ FOXP3+ Treg cells, whereas the A subtype showed lower levels of Treg cells. CONCLUSION: Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC who were treated with regorafenib plus nivolumab might be of value for predictive clinical benefit. Further studies are needed to evaluate the predictive role of Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC.
