Background: It remains controversial whether patients with EGFR-mutant lung adenocarcinoma should stop using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after progression during treatment.
Case report: We report a 35-year-old man with poorly differentiated adenocarcinoma of the left upper lobe and an exon 19 deletion (Ex19Del) mutation found by large-panel next-generation sequencing. The patient underwent video-assisted thoracoscopic surgery 12 months after oral administration of icotinib 125 mg tid, and the left upper lobe and surrounding lymph nodes were removed. Postoperative pathology supported a diagnosis of left upper lobe adenocarcinoma and subcarinal (1/2), main pulmonary artery window (1/2), and left hilar (1/2) lymph node metastases. The EGFR mutations in the residual lesions had disappeared, and Ex19Del mutations were still visible in the mediastinal lymph node metastasis.
Conclusion: Spatial heterogeneity of the resistance mechanism may explain why patients who continue to receive EGFR-TKIs in combination with local therapies (e.g., radiotherapy) for progressing lesions may benefit even after progression during EGFR-TKI therapy. The loss of the EGFR mutation allele as a putative resistance mechanism requires additional preclinical and clinical confirmation.
Keywords: EGFR-TKI; Lung adenocarcinoma; acquired resistance; genetic mutation; spatial heterogeneity.