Prolonged survival in EGFR exon 20 insertion mutant lung adenocarcinoma: case report of sequential osimertinib and furmonertinib with research trend analysis

TL;DR

A patient with a rare lung cancer mutation lived longer with high-dose targeted drugs, suggesting new treatment possibilities.

Contribution

A case report showing prolonged survival with sequential high-dose EGFR-TKIs in EGFR exon 20 insertion mutant lung cancer.

Findings

A patient with EGFR exon 20 insertion mutation achieved durable response with high-dose osimertinib followed by furmonertinib.

Overall survival of approximately 37 months was observed with sequential high-dose third-generation EGFR-TKIs.

Bibliometric analysis shows increasing global research focus on variant-specific treatments for EGFR exon 20 insertion mutations.

Abstract

Epidermal growth factor receptor (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 ex20ins subtypes, yet real-world data are scarce.

We describe a 56-year-old never-smoking female with metastatic lung adenocarcinoma harboring an EGFR A767_V769dup exon 20 insertion and co-mutations in TP53, SETD2, SMAD4, and ETV6, with low PD-L1 expression. In the setting of limited access to amivantamab at diagnosis and preliminary evidence supporting intensified EGFR inhibition in certain “near-loop” ex20ins variants, the patient received off-label high-dose osimertinib 160 mg once daily as first-line therapy. She achieved a durable partial response with manageable Grade 1 skin and nail toxicities and no dose reductions. Following disease progression, and after multidisciplinary discussion and informed consent, she was switched to off-label furmonertinib 240 mg once daily, resulting in additional disease control. Sequential high-dose osimertinib followed by high-dose furmonertinib yielded an overall survival of approximately 37 months.

To contextualize this case, we conducted a targeted narrative review and a descriptive bibliometric overview using CiteSpace (2000–2023) based on Web of Science Core Collection records. This analysis demonstrated a growing global research focus on third-generation EGFR-TKIs and variant-specific treatment strategies for EGFR ex20ins-mutant NSCLC, supporting the rationale underpinning the therapeutic approach adopted in this report.

Sequential high-dose third-generation EGFR-TKIs may offer clinically meaningful benefit in selected EGFR ex20ins cases; however, this strategy remains non-standard and should be regarded as hypothesis-generating, warranting further prospective evaluation.

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