Activity of osimertinib in a patient with stage IV non-small cell lung cancer harboring HER2 exon 19, p.L755P mutation: case report

Background: Recurrent in-frame insertions within exon 20 causing duplication of amino acids TyrosineValine-Methionine-Alanine (YVMA) represent 80% of all HER2 alterations in non-small cell lung cancer (NSCLC). HER2 tyrosine kinase inhibitors (TKI), anti-HER2 monoclonal antibodies and HER2 directed antibody-drug conjugates have been evaluated in patients with HER2 mutated NSCLC. Limited data are available regarding the activity of these agents in exon 19 alterations. Osimertinib, a 3rd generation EGFRTKI, has been found in pre-clinical studies to decrease growth of NSCLC with HER2 exon 19 aberrations. Case Description: A 68-year-old female with a past medical history of type 2 diabetes and minimal smoking was diagnosed with stage IV NSCLC. Next generation sequencing on tumor tissue demonstrated an ERBB2 exon 19 c.2262_2264delinsTCC, p.(L755P) mutation. After five lines of treatment that included chemotherapy, chemoimmunotherapy and investigational agents the patient's disease was progressing. At this time her functional status remained good, therefore clinical trials were explored however, none were available. Based on findings from pre-clinical studies, the patient was commenced on osimertinib 80 mg OD and achieved a partial response (PR) according to RESIST criteria both intra- and extracranially. Conclusions: This is the first report to our knowledge to demonstrate activity of osimertinib in a patient with NSCLC harboring HER2 exon 19, p. L755P mutation resulting in intra- and extracranial response. In the future, osimertinib could become a targeted treatment for patients harboring Exon19 ERBB2 point mutations.