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Cell Rep Med ; 5(7): 101615, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38897205

ABSTRACT

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8+ regulatory T (Treg)hi/CXCL13+ exhausted T (Tex)lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Lung Neoplasms , Mutation , Neoadjuvant Therapy , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Neoadjuvant Therapy/methods , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Female , Male , Middle Aged , Aged , Mutation/genetics , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Paclitaxel/therapeutic use , Carboplatin/therapeutic use , Adult , Treatment Outcome , Circulating Tumor DNA/genetics , Albumins
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