A Case of Lung Adenocarcinoma With Concurrent EGFR Mutation and ALK Fusion Combined With Literature Review

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Epidermal growth factor receptor (EGFR) mutations are common drivers in lung adenocarcinoma.
• EGFR-tyrosine kinase inhibitors (TKIs) are standard first-line treatments but acquired resistance is inevitable.
• Mechanisms of acquired resistance, including gene fusions, necessitate ongoing monitoring.

Purpose of the Study:

• To highlight the importance of retesting for resistance mechanisms in EGFR-mutant lung adenocarcinoma.
• To demonstrate the clinical benefit of early identification and targeted therapy switch.

Main Methods:

• Case report of a patient with EGFR-mutant lung adenocarcinoma.
• Utilized molecular testing to identify resistance mechanisms upon disease progression.
• Administered alectinib, an anaplastic lymphoma kinase (ALK) inhibitor, after identifying EML4-ALK fusion.

Main Results:

• The patient experienced rapid progression despite initial EGFR-TKI therapy.
• Retesting revealed a co-occurring EML4-ALK fusion, a mechanism of resistance.
• Switching to alectinib resulted in rapid and sustained clinical improvement.

Conclusions:

• Acquired resistance mechanisms, such as EML4-ALK fusion, can coexist with primary EGFR mutations in lung adenocarcinoma.
• Proactive retesting for resistance is essential for optimizing treatment strategies.
• Targeted therapy with alectinib is effective in patients with EML4-ALK fusion following EGFR-TKI failure.