Case Report: A Rare EGFR 20 Insertion Variant, P772_H773insGNP Mediates Resistance to Sunvozertinib but Is Sensitive to Furmonertinib

Yufang Wang, Jing Zheng, Jie Wang, Lingyan Sheng, Jingjing Qu, Jianya Zhou Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Jianya Zhou, Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Tel/Fax +86 571 8723 6876, Email [email protected]: EGFR exon 20 insertion (Exon 20ins) is the most common type among rare EGFR mutations. It involves over 100 identified subtypes. These mutations are generally insensitive to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). The development of small-molecule targeted agents specifically designed for Exon 20ins has brought new hope to this patient population. However, responses to Exon 20ins targeting agents vary across different insertion subtypes, and there is currently a lack of research focused on treatment strategies specifically for near-loop mutations such as P772_H773insGNP.Methods: To explore individualized treatment strategies, we reviewed the medical records of a patient with Exon 20ins P772_H773insGNP. Relevant medical history, laboratory and imaging findings, and treatment details were collected and analyzed.Results: This case report describes a patient with advanced non-small cell lung cancer (NSCLC). The patient was diagnosed with adenocarcinoma of the right upper lobe (T3N1M1a, stage IV). Next-generation sequencing (NGS) detected an EGFR exon 20ins, specifically P772_H773insGNP. The patient experienced disease progression despite multiple lines of therapy. Following multidisciplinary discussion, furmonertinib was initiated as sixth-line therapy. The best overall response was assessed as partial response (PR), and as of the last follow-up, the patient had achieved a progression-free survival (PFS) of 10.5 months.Conclusion: This case represents the first report of a favorable response to furmonertinib in a patient with the EGFR exon 20ins subtype P772_H773insGNP, a near-loop mutation. EGFR exon 20ins mutations are highly heterogeneous, and different subtypes exhibit varying sensitivities to targeted drugs. Exploring individualized treatment approaches is of great clinical importance.Keywords: EGFR 20 insertion, non-small cell lung cancer, rare subtype, sunvozertinib, furmonertinib, case report