Tumour immune and metabolic profiling identifies biomarkers of avelumab benefit in MSS mCRC

In this video, Elena Benidovskaya presents translational findings from the AVETUXIRI trial, which evaluated avelumab combined with cetuximab and irinotecan in 55 patients with chemorefractory, microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) and liver or lung metastases, a population generally resistant to immune checkpoint inhibition.¹ The analysis explored tumour- and blood-based correlates of treatment benefit.

In metastatic biopsies, baseline rather than treatment-induced infiltration of CD3+ and CD8+ T cells was associated with improved survival, a finding supported by RNA sequencing. Deconvolution analysis and immunofluorescence further suggested a potential role for intratumoural B-cell infiltration in responding patients. In contrast, non-responding tumours showed greater activation of metabolic signalling pathways.

In blood, flow cytometry showed no baseline differences between responders and non-responders, but an on-treatment increase in circulating NKT-cell frequency was associated with better outcomes. CD3+ and CD8+ T-cell findings from tissue were not recapitulated in blood.