Female,58 years old, had no smoking history without relevant personal or family medical history. In June 2015, she was diagnosed with lung adenocarcinoma cT1bN2M0...Blood detection showed PIK3CA gene mutation….Combined with the results of cerebrospinal fluid cytology, she was diagnosed as LM. Considering tumor heterogeneity, we recommended her to have CSF ctDNA testing, as a result of EGFR L858R mutation. She started aumolertinib (110mg qd oral) and pemetrexed (0.75g d1 ivgtt ,21d/cycle, 10cycles) getting headache relief. Until CSF ctDNA EGFR mutation abundance increased from 22.7% to 42.4% in April, 2021, intrathecal pemetrexed was given as supplementary treatment for acute exacerbations....Under this treatment plan, the patient has achieved a progression-free survival of more than 25 months and a good quality of life....Aumolertinib combined with metronomic intrathecal pemetrexed can improve the curative effect of LM and achieve long-survival time.