Response to Afatinib in a Common EGFR-Mutated Lung Adenocarcinoma with a Very Rare Combination of Compound Mutations.

A 76-year-old woman was referred to our hospital due to a nodule detected by mass screening. Biopsy specimens from the lesion showed epidermal growth factor receptor (EGFR)-mutated (exon 21 858R) adenocarcinoma. She underwent surgical resection; however, a year later, intrapulmonary metastases were discovered. Therefore, afatinib therapy was initiated as first-line therapy. The best response to afatinib was evaluated as “partial response,” and progression-free survival (PFS) was 24 months. Then, she received chemotherapy for 6 months, erlotinib and bevacizumab for 5 months, and nivolumab for 3 months. After these treatments, pleural dissemination and accumulation of pleural fluid developed. EGFR mutation was re-evaluated using cancer cells in the pleural fluid to confirm the presence or absence of the T790M gene mutation. Cytological diagnosis was adenocarcinoma, and T790M gene was not detected. Afatinib was given for 3 months, but the best therapeutic effect was “stable disease,” and the patient died 4 months after re-administration of afatinib. Overall survival was 42 months. We undertook a detailed analysis of compound mutations and the content ratio of tumor cells and relative allele frequency (RAF) in pathological specimens obtained by surgical resection using Non-overlapping Integrated Read Sequencing System (NOIR-SS) (DNA Chip Research Inc. Tokyo, Japan). 1,2 Briefly, DNA was extracted from the slices of formalin fixed paraffin embedded (FFPE) tissue block of the patient using a Maxwell® RSC DNA FFPE kit (Promega, Madison, Wis, USA). 50 ng of DNAs were fragmented by Covaris focus ed-ul traso nicat or (Woburn, Mass, USA), and molecular-barcoded of patients with complicated EGFR mutation backgrounds as this patient. Satoh H, Miyazaki K, Sato Y, Hizawa N. Response to afatinib in a common EGFR-mutated lung adenocarcinoma with a very rare combination of compound mutations. Turk Thorac 2022;23(5):364-365.