Case report: EGFR fusion mutation combined with EGFR amplification responds to EGFR-TKI therapy

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for non-small cell lung cancer (NSCLC) with common EGFR-sensitive mutations.
• EGFR fusion mutations and EGFR amplification are exceedingly rare in NSCLC, with limited data on their clinical significance and treatment response.

Observation:

• This report details two NSCLC patients presenting with concurrent rare EGFR fusion mutations (EGFR-MACF1 and EGFR-GNAT3) and EGFR amplification.
• Both patients were treated with EGFR-TKI therapy, a standard treatment for common EGFR mutations.

Findings:

• One of the two patients with rare EGFR alterations (fusion and amplification) exhibited a notable antitumor response to EGFR-TKI treatment.
• The findings suggest a potential, albeit limited, role for EGFR-TKIs in a subset of NSCLC patients with these uncommon genetic profiles.

Implications:

• These cases highlight the importance of comprehensive genomic profiling to identify rare EGFR alterations in NSCLC.
• Further research is warranted to understand the efficacy and optimal management strategies for NSCLC patients with combined EGFR fusion and amplification mutations.