Tumor microenvironment modifications induced by afatinib in squamous cell carcinoma of the head and neck - a window-of-opportunity study (EORTC90111-24111)

The EORTC-90111-24111 window study included treatment-naïve patients with primary HNSCC receiving afatinib versus no preoperative treatment. We found that treated patients had an increase in tumor CD3+ density and CD3+ and CD8+ T-cell infiltration compared to control patients. Afatinib- exposed tumor had upregulation of gene expression signatures predictive of response to PD-1 blockade. Also, we observed two clusters among treated patients. Cluster 1 showed a higher expression of markers and gene sets implicated in epithelial-to-mesenchymal transition and cancer-associated fibroblasts activation after afatinib compared to cluster 2 and controls. These results open perspectives to overcome resistance mechanisms to anti-HER therapy and to potentiate the activity of immune checkpoint inhibitors. Thirty treatment-naïve patients with primary HNSCC were randomized. Twenty-five patients received afatinib for 14 days before surgery (40mg 1x/day) and five patients were attributed to the control arm. Biopsies were taken at work-up and during surgery. Good quality RNA samples were used for omics analyses (n=13 in treated patients)