Efficacy of methotrexate combined with furmonertinib in treatment of osimertinib-resistant patients with brain metastasis from lung cancer

Wang Pengkun; Cao Fei; Li Pengfei

doi:10.3969/j.issn.1672-8157.2025.06.022

Abstract：Objective To investigate the clinical efficacy and safety of methotrexate combined with furmonertinib in treatment of patients with brain metastasis from epidermal growth factor receptor(EGFR)-mutated lung cancer after osimertinib resistance.Methods A total of 98 osimertinib-resistant patients with brain metastasis from EGFR-mutated lung cancer who were admitted to the First People's Hospital of Pingdingshan from January 2023 to December 2024 were enrolled and divided into two groups using a random number table method.The control group(n=49)received furmonertinib monotherapy,while the observation group(n=49)was given a combination therapy of methotrexate and furmonertinib.The clinical efficacy,laboratory indicators(serum carcinoem-bryonic antigen(CEA)and vascular endothelial growth factor(VEGF)),survival period,and the incidence of adverse reactions were compared between the two groups.Results After 2 months of treatment,the intracranial disease control rate(IDCR)and objec-tive response rate(ORR)in the observation group(79.59%(39/49)and 57.14%(28/49),respectively)were higher than those in the control group(61.22%(30/49)and 34.69%(17/49),respectively)(χ2=3.967,4.972,both P<0.05).The levels of CEA and VEGF in both groups decreased after treatment,and the levels of these indicators in the observation group((8.32±1.26)ng·mL-1 and(87.49±9.63)μg·L-1,respectively)were lower than those in the control group((12.05±1.84)ng·mL-1 and(108.63±14.27)μg·L-1,respec-tively)(t=11.708,8.596,both P<0.05).As of the end of follow-up in March 2025,there were 37 cases in disease progression in the observation group and 41 cases in the control group.The median progression-free survival(PFS)in the observation group was 10.00 months,which was longer than 5.50 months in the control group(Log-rank χ2=4.005,P=0.045).There were 30 deaths in the observation group and 39 in the control group.The median overall survival(OS)reached 15.00 months in the observation group,longer than 10.00 months in the control group.(Log-rank χ2=5.877,P=0.015).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion Methotrexate combined with furmonertinib in the treatment of patients with brain metastasis from EGFR-mutated lung cancer after osimertinib resistance can improve the intracranial lesion control rate,reduce the levels of tumor markers,and prolong survival time,demonstrating favorable safety profile.