PMC7871906_01
Patient 1 case history and time line of key events. PD, progressive disease; SD, stable disease.
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Molecular pathology based on Sanger sequencing of EGFR exons 18 to 21 indicated no EGFR mutation, and the tumor was ALK fluorescence in situ hybridization negative and ROS1 immunohistochemistry-negative ( Figure 2 ).
Patient 1 clinical course, including treatment history and CT scans. CT, computed tomography.
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The scan revealed several pulmonary focal ground-glass opacities (GGOs) in both lungs, some of which had increased in size compared with preoperative CT findings ( Figure 3 ). She remained on treatment with afatinib (20 mg/day) and had stable disease again from July 2016 until July 2017 ( Figure 3 ), when progression ensued and she received stereotactic irradiation to one lesion in the left lower lobe. Treatment with afatinib is ongoing as of October 2020, and the patient continues to have stable disease ( Figure 3 ), with an Eastern Cooperative Oncology Group performance status of 0.
Insertion site of EGFR exon 20 insertion mutation. Sequencing electropherogram of EGFR exon 20 showing: (A) wild-type sequence of the adenocarcinoma from patient 1 resected in 2014; (B) duplication of a CAC base triplet in the adenocarcinoma from patient 1 biopsied in 2015. EGFR, epidermal growth factor receptor; CAC, cytosine adenine cytosine; (C) wild-type sequence of the adenocarcinoma from patient 2 resected in 2019; (D) duplication of a CAC base triplet in the adenocarcinoma from patient 2 biopsied in 2019.
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Figures 4A, B  ). From July 2015, the patient received afatinib 40 mg/day, which was reduced to 30 mg/day in August 2015 and further reduced to 20 mg/day in October 2015 due to diarrhea. Histology revealed invasive adenocarcinoma, and NGS with the Oncomine Focus Assay (Thermo Fisher Scientific) identified an EGFR exon 20 insertion (NM_005228.3 [EGFR]: codon 2317_2319dupCAC; p.H773dup;  Figures 4C, D ) that was identical to the mutation identified in Patient 1.