Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.605853
Keywords
afatinib; EGFR-KDD; lung adenocarcinoma; next-generation sequencing; tyrosine kinase inhibitor
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Funding
- National Natural Science Foundation of China [U1609220]
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The efficacy of EGFR-TKIs in patients with rare EGFR mutations such as EGFR-KDD remains unclear, although case reports have shown variable antitumor responses. Treatment with afatinib in a 61-year-old male with T1N3M0 LUAD harboring EGFR-KDD resulted in partial response with a progression-free survival of 12 months and counting, providing clinical evidence for EGFR-TKI administration in advanced LUAD patients with EGFR-KDD.
The rapid development of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations including but not limited to exon 19 deletions (19 del) and point mutation L858R in exon 21. However, the efficacy of EGFR-TKIs in patients with rare mutations, such as EGFR-kinase domain duplication (KDD), remains elusive. EGFR-KDD often results from in-frame tandem duplication of EGFR exons 18-25, causing subsequent constitutive activation of EGFR signaling. Several case reports have revealed the efficacies of EGFR-TKIs in advanced lung adenocarcinoma (LUAD) with EGFR-KDD but yielded variable antitumor responses. In the present study, we report a 61-year-old male patient diagnosed with T1N3M0 (stage IIIB) LUAD harboring EGFR-KDD involving exons 18-25. He was treated with afatinib and achieved partial response (PR) with progression-free survival (PFS) of 12 months and counting. Our work, confirming EGFR-KDD as an oncogenic driver and therapeutic target, provides clinical evidence to administer EGFR-TKIs in patients with advanced LUAD harboring EGFR-KDD.
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