Successful treatment of a lung adenocarcinoma patient with a novel EGFR exon 20-ins mutation with afatinib: A case report

Abstract

Rationale: Comprehensive genomic profiling for non-small cell lung cancer (NSCLC) is likely to identify more patients with rare genetic alterations, including uncommon epidermal growth factor receptor (EGFR) gene mutation.

Patient concerns: A 63-year-old Chinese woman who had never smoked visited our lung cancer clinic due to a chronic cough.

Diagnosis: The patient was diagnosed with lung adenocarcinoma by transbronchial lung biopsy. An EGFR mutation (exon 20 insertion H773_V774insH, D770_N771insG, V769_D770insASV, D770_N771insSVD) was detected in the biopsy specimen by quantitative real-time PCR.

Interventions: The patient was treated with osimertinib first, and the progression-free survival (PFS) was 4.4 months. After the disease progressed, the second genetic test of pleural effusion suggesting the EGFR exon 20-ins mutation site changed to A767delinsASVD only. Then the patient was treated with afatinib with informed consent.

Outcomes: The treatment of afatinib in this patient was successful, PFS was 7.4 months.

Lessons: To our knowledge, EGFR exon 20-ins mutation A767delinsASVD has never been reported, and the successful treatment of afatinib may provide a new therapeutic option for this type of exon 20 insertion mutations.

Figure 1

Insertion site of EGFR exon20 insertion mutants. (a) Previous reported Exon 20 insertion mutations. Prevalence of each mutation spectrum (noted as insX to represent all known insertions within those residues) by amino acid position is indicated in parentheses. (b) Gene analysis and MA from sequential tumor biopsy specimens by quantitative real-time PCR before treated with osimertinib. (c) Gene analysis and MA; amplified gene shows only AT from pleural effusion by NGS of the whole-exome after treatment with osimertinib. AT = amplification time, EGFR = epidermal growth factor receptor, MA = mutation abundance, NGS = next generation sequencing.

Figure 2

Patient clinical course including treatment history and relevant imaging studies. (1) At baseline before osimertinib, showing left pulmonary lesion and left pleural effusion. (2) At 1.5 months of osimertinib, with an SD response. (3) At 2.5 months of osimertinib, with an SD response. (4) At 4.4 months of osimertinib, lung and left pleural effusion progression. (5) At 4.0 months of treatment with afatinib, left pulmonary lesion was stable disease and the pleural effusion was significantly reduced. (6) At 7.4 months of treatment with afatinib, with progressed disease with left pulmonary lesion and stable pleural effusion. SD = Stable Disease.