I have a newly diagnosed stage IVB NSCLC (adeno) with primarily skeletal and lung disease. Her biopsy has returned as a poorly differentiated adenocarcinoma. Molecular data include PD-L1 TPS <1%, EGFR G719A, ERBB2 p.S310F. No other actionable mutations. She is still post operative from her spinal decompression and ECOG 2. Should I target her uncommon EGFR mutation or Her2 mutation up front?

Lung Cancer Specialist

This is an interesting case. EGFR G719A is a PACC mutation Han, C., Ding, X., Li, M. et al. Afatinib, an effective treatment for patient with lung squamous cell carcinoma harboring uncommon EGFR G719A and R776C co-mutations. J Cancer Res Clin Oncol 148, 1265–1268 (2022). Preclinical work and cohorts suggest it would respond best to a second generation EGFR tyrosine kinase inhibitor like afatinib. afatinib also has HER2 activity so that would be my first choice here.