Prolonged Survival in EGFR Exon 20 Insertion Mutant Lung Adenocarcinoma: Case Report of Sequential Osimertinib and Furmonertinib with Research Trend Analysis

Yishan Lu¹Ruiguo Zhao²Ning Wang²Jingjing Zhao²Nana Huang³ABDULLAH AL-DANAKH⁴Haijing Liu⁵Ping Gao^1*

• ¹Department of oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
• ²The second affiliated hospital of dalian medical university, department of oncology, DALIAN, China
• ³Liaoning Cancer Hospital and Institute, Shenyang, China
• ⁴Department of Urology, Amran University, 'Amran, Yemen
• ⁵department of integrative medicine, Central South University Xiangya School of Medicine, Changsha, China

Background: EGFR exon 20 insertion (ex20ins)–mutant non–small cell lung cancer (NSCLC) is characterized by limited sensitivity to standard-dose EGFR tyrosine kinase inhibitors (EGFR-TKIs) and historically poor clinical outcomes. Although agents such as amivantamab and other targeted therapies have expanded treatment options, access barriers and marked variant-specific heterogeneity remain major challenges. Emerging evidence suggests that dose-escalated third-generation EGFR-TKIs may provide clinical benefit in selected exon 20 insertion subtypes, yet real-world data remain scarce. Case presentation: We describe a 56-year-old female with advanced NSCLC harboring an EGFR exon 20 insertion mutation (A767_V769dup). She achieved 12 months of progression-free survival on high-dose osimertinib (160 mg), followed by disease control with furmonertinib (240 mg), reaching a total overall survival of 37 months with good tolerance. The tumor exhibited low PD-L1 expression and low tumor mutational burden, while next-generation sequencing revealed co-mutations in TP53, SETD2, SMAD4, and ETV6. Dose-escalated third-generation TKIs were selected after multidisciplinary discussion and patient-informed consent because of limited access to amivantamab and the variant’s structural features, which may confer partial sensitivity at higher drug exposure. Conclusion: This case illustrates prolonged survival achieved through sequential high-dose osimertinib and furmonertinib in a patient with the near-loop EGFR A767_V769dup variant. The report highlights the potential role of dose-escalated third-generation TKIs in select exon 20 insertion subtypes, the influence of real-world access limitations, and the importance of individualized, mutation-specific therapeutic strategies. Larger prospective studies are needed to validate these observations.