Fam-Trastuzumab-Deruxtecan and Osimertinib Combination to Target HER2 Driven Resistance in a Patient With NSCLC After Osimertinib Progression: Case Report

HER2 mutations have been identified as potential mechanisms of resistance to EGFR-directed therapies in patients with advanced or metastatic NSCLC. Here, we report the case of a 65-year-old female with metastatic, EGFR exon 19–mutant NSCLC initially treated with first-line osimertinib. After several subsequent lines of treatment including erlotinib and carboplatin+pemetrexed+osimertinib, repeat genetic sequencing identified a HER2 exon 20 insertion (A775_G776insYVMA) in both blood and tissue. She was treated using fam-trastuzumab-deruxtecan, which resulted in a disease response lasting for 8 months. This report represents the first published case detailing the safety and efficacy of a combination fam-trastuzumab-deruxtecan and osimertinib in a patient with NSCLC and HER2-mutated resistance after EGFR-targeted therapy. The findings from this report suggest that fam-trastuzumab-deruxtecan can be safely given in combination with osimertinib and should be considered as subsequent-line therapy for patients who progress on osimertinib and develop a HER2 resistance mutation.