Here, we report on a case of lung adenocarcinoma with brain metastases harboring compound mutations in EGFR exon 21 Leu858Arg and mitogen-activated protein kinase 1 (MEK1) exon 3 lle112Thr and with a high program death ligand 1 (PD-L1) expression who responded well to combination therapy (targeted therapy with furmonertinib, chemotherapy with pemetrexed and lobaplatin, and immunotherapy with tislelizumab), successfully achieving a pathological complete response. The gene discussed is MAP2K1; the disease is lung adenocarcinoma.