Nonsmall cell lung cancer with rare exon 7 p.A289V mutation in the EGFR gene responds to Icotinib treatment: A case report

Abstract

Rationale: Mutation p.A289V involving extracellular region of epidermal growth factor receptor (EGFR) exon 7 has not yet been reported in nonsmall cell lung cancer (NSCLC). Studies have shown p.A289V mutation responding to tyrosine kinase inhibitors (TKIs) in glioblastoma cell lines suggesting the point mutation as a potential therapeutic target. However, sufficient evidence of the effect of TKI treatment on the p.A289V mutation involved in NSCLC is not available.

Patient concerns: An 80-year-old nonsmoker male with lung mass was suffering from severe bone pain.

Diagnosis: Needle biopsy and positron emitted tomography/computed tomography were performed. The patient was diagnosed with advanced NSCLC adenocarcinoma with bone and lymphatic metastasis. Next-generation sequencing of circulating tumor DNA was performed, which identified a p.A289V mutation in the EGFR gene of the patient.

Interventions: Our patient refused to receive chemotherapy and tried Icotinib treatment.

Outcomes: Our patient had a partial response to Icotinib after treatment for 5 months during the therapeutic trial by TKIs. The patient showed adverse symptoms of mild diarrhea and rash (Common Terminology Criteria for Adverse Events grade 1) during the treatment.

Lessons: In this case, Icotinib prevented completion of the signal transduction cascade of p.A289V mutant in NSCLC. Our finding may expand the EGFR mutation spectrum for TKI treatment in NSCLC. However, the finding needs to be confirmed at a larger scale with NSCLC in Chinese and other populations.

Figure 1

(A) Positron Emission Tomography–Computed Tomography scans showed primary and metastatic lesions of lung cancer. Hypermetabolic signals were found in tumor mass in left upper lobe of lung, posterior section of the left 6th rib, 2nd lumbar vertebral body, 3rd sacral vertebral body, middle segment of right femur, and multiple lymph nodes; (B) histochemical stain of tumor tissue showed mucinous adenocarcinoma (hematoxylin–eosin ×100); (C) next-generation sequencing data of circulating tumor DNA indicated a somatic mutation EGFR p.A289V (c.866C>T), minor allele T accounted for 0.61%. EGFR = epidermal growth factor receptor.

Figure 2

Computed tomography scans of the chest showed: (A) before Icotinib therapy; (B) tumor volume and mediastinal lymph nodes slightly decreased after 1 month of Icotinib; (C) tumor volume and mediastinal lymph nodes significantly decreased, and the patient had a partial response after 5 months of Icotinib. Yellow arrow indicated primary lung mass; yellow arrow with rectangle indicated multiple metastatic lymph nodes.

Figure 3

EGFR exon 7 p.A289V missense mutation in the extracellular domain. It shows dimerized EGFR molecules bound by the EGF ligand. The position of the common sensitive mutations is indicated along with the downstream effectors activated by EGFR autophosphorylation-STAT3, MAP kinase (MAPK), and AKT. The newly discovered p.A289V mutation in nonsmall cell lung cancer is shown in orange. EGFR = epidermal growth factor receptor.