Multi-omics characterization of response to tyrosine kinase inhibitor plus immunotherapy in MSS/pMMR metastatic colorectal cancer: A multicenter biomarker study.

206 Background: Patients with refractory microsatellite-stable metastatic colorectal cancer (MSS mCRC), representing the vast majority of mCRC cases, derive minimal benefit from immune checkpoint inhibitor (ICI) monotherapy. Combining anti-angiogenic tyrosine kinase inhibitors (TKIs) with ICIs has emerged as a promising strategy to overcome resistance. Methods: This multicenter retrospective study compared the efficacy and safety of anlotinib plus tislelizumab (n=65) versus anlotinib monotherapy (n=59) in patients with refractory MSS mCRC. Integrative whole-exome sequencing (WES), RNA sequencing, and multiplex immunohistochemistry (mIHC) were performed on pre-treatment tumor samples (n=29 from the combination group) to identify biomarkers of response. Immunotherapy response was defined as complete response (CR), partial response (PR), or stable disease (SD) lasting ≥6 months. Results: Combination therapy significantly improved median progression-free survival (196 vs 122 days, P =0.028) and median overall survival (453 vs 245 days, P