The effect of afatinib in a pretreated patient with invasive mucinous adenocarcinoma of the lung harboring HER2 YVMA insertion: a case report

Background: Invasive mucinous adenocarcinoma (IMA) is an uncommon variant of lung adenocarcinoma. The survival data and therapeutic methods for IMAs are limited. The frequency of human epidermal growth factor receptor 2 ( HER2 ) mutations in IMAs is low, and the clinical benefit of HER2 inhibitors in patients with IMA is still being explored. Afatinib is a pan-HER inhibitor and the studies of afatinib treatment in IMA patients are very limited. Case Description: Herein, we present the case of a 49-year-old female, never-smoker stage IVa IMA patient with persistent cough and sputum expectoration diagnosed with stage IVa IMA. Polymerase chain reaction (PCR) and next-generation sequencing (NGS) were utilized to detect mutations for targeted therapies on lung biopsy, but no mutation was found. After treatment failures of chemotherapy and a multiple-kinase inhibitor, liquid biopsy identified HER2 exon 20 insertion p.A775_G776insYVMA with NGS. The patient was then treated with afatinib as the third-line treatment. Following administration for one month, the patient’s symptoms of coughing, sputum expectoration, and dyspnea improved. Stable disease (SD) was observed, and the patient achieved durable clinical benefit with prolonged progression-free survival (PFS) of 20 months. Her overall survival was 5.8 years. Conclusions: This is the first report of afatinib treatment achieving long-lasting and stable disease control in an IMA patient with a HER2 exon 20 YVMA insertion. Our results will help to improve the treatment of IMA.