Brief Report: EGFR L833V/H835L Duplex-Mutated NSCLC With Leptomeningeal Carcinomatosis Responsive to Osimertinib

•Non–small-cell lung cancer harboring the duplex EGFR exon 21 L833V/H835L mutation is rare but exhibits sensitivity to EGFR TKI (tyrosine kinase inhibitor) therapy. •We report a case of this mutation in lung adenocarcinoma with leptomeningeal carcinomatosis which demonstrated an exceptional response to the EGFR TKI osimertinib. •Clinicians should be aware of the potentially actionable nature of the EGFR L833V/H835L mutation and consider treatment with a TKI such as osimertinib. •Non–small-cell lung cancer harboring the duplex EGFR exon 21 L833V/H835L mutation is rare but exhibits sensitivity to EGFR TKI (tyrosine kinase inhibitor) therapy. •We report a case of this mutation in lung adenocarcinoma with leptomeningeal carcinomatosis which demonstrated an exceptional response to the EGFR TKI osimertinib. •Clinicians should be aware of the potentially actionable nature of the EGFR L833V/H835L mutation and consider treatment with a TKI such as osimertinib.