Data from Tumor Microenvironment Modifications Induced by Afatinib in Squamous Cell Carcinoma of the Head and Neck: A Window-of-Opportunity Study (EORTC-90111–24111)

Axelle E Loriot,Pamela Baldin,Antonella Mendola,Lisa F Licitra,Nicolas D Huyghe,Paul M Clement,Anne-Sophie Govaerts,Catherine Fortpied,Simon P Beyaert,Jean-Pascal H Machiels,Sandra Schmitz,Rose-Marie Goebbels,Yassine Lalami

doi:10.1158/1078-0432.c.6879401.v1

Abstract

<div>AbstractPurpose:The EORTC-90111–24111 phase II window study evaluated afatinib versus no preoperative treatment in patients with primary squamous cell carcinoma of the head and neck (HNSCC). We investigated afatinib-induced tumor and microenvironment modifications by comparing pre- and posttreatment tumor biopsies.Patients and Methods:Thirty treatment-naïve patients with primary HNSCC were randomized. Twenty-five patients received afatinib for 14 days before surgery (40 mg 1×/day) and 5 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. The control arm was enlarged by samples coming from our previous similar window study.Results:IHC analyses of afatinib-treated tumor biopsies showed a decrease in pEGFR (P ≤ 0.05) and pERK (P ≤ 0.05); and an increase in CD3+ (P ≤ 0.01) and CD8+ (P ≤ 0.01) T-cell infiltration, and in CD3+ (P ≤ 0.05) T-cell density. RNA sequencing analyses of afatinib-treated tumor samples showed upregulation of inflammatory genes and increased expression scores of signatures predictive of response to programmed cell death protein 1 blockade (P ≤ 0.05). In posttreatment biopsies of afatinib-treated patients, two clusters were observed. Cluster 1 showed a higher expression of markers and gene sets implicated in epithelial-to-mesenchymal transition (EMT) and activation of cancer-associated fibroblasts (CAF) compared with cluster 2 and controls.Conclusions:Short-term treatment with afatinib in primary HNSCC induces CD3+ and CD8+ tumor infiltration and, in some patients, EMT and CAF activation. These results open perspectives to overcome resistance mechanisms to anti-HER therapy and to potentiate the activity of immune checkpoint inhibitors.</div>

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