Different Tyrosine Kinase Inhibitors Used in Treating EGFR-Mutant Pulmonary Adenocarcinoma with Brain Metastasis and Intracranial Intervention Have No Impact on Clinical Outcomes

SIMPLE SUMMARY: Brain metastasis is a factor of a poor prognosis in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The standard treatment is systemic therapy combined with intracranial intervention, such as craniotomy or radiotherapy. However, intracranial intervention may result in neurological or cognitive deficiency. We conducted a retrospective study to determine the optimal treatment strategy for EGFR-mutant NSCLC patients with brain metastasis receiving or not receiving intracranial intervention. Intracranial intervention had no statistically significant impact on response rate (RR), progression-free survival (PFS), or overall survival (OS) of patients with EGFR mutations and brain metastasis who received EGFR tyrosine kinase inhibitors (TKIs) as a first-line therapy. Treatment with different EGFR TKIs did not result in significant differences in RR or OS, but PFS differed significantly between the therapies. Afatinib and osimertinib both showed significantly longer PFS than gefitinib in a Cox regression model. The OS of patients with higher graded prognostic assessment (GPA) scores was significantly longer. Physicians should be vigilant about patients who have lower GPA scores at initial diagnosis of NSCLC with brain metastasis. ABSTRACT: Brain metastasis in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is a factor of poor prognosis. We conducted a retrospective study to determine the optimal treatment strategy for EGFR-mutant NSCLC patients with brain metastasis receiving or not receiving intracranial intervention. A total of 186 patients treated with an EGFR TKI were enrolled in the study, and 79 (42%) received intracranial intervention. Patients who received intracranial intervention and those who did not had a similar treatment response rate (RR), progression-free survival (PFS) (median PFS: 11.0 vs. 10.0 months, p = 0.4842), and overall survival (OS) (median OS: 23.0 vs. 23.2 months, p = 0.2484). Patients treated with gefitinib, erlotinib, afatinib, or osimertinib had a similar RR (63%, 76%, 81%, or 100%, respectively, p = 0.1390), but they had significantly different PFS (median PFS: 7.5, 10.0, 14.8 months, or not reached, respectively, p = 0.0081). In addition, OS tended to be different between different EGFR TKI treatments (median OS of 19.2, 23.7, or 33.0 months for gefitinib, erlotinib, or afatinib treatments, respectively, p = 0.0834). Afatinib and osimertinib both demonstrated significantly longer PFS than gefitinib in a Cox regression model. Graded prognostic assessment (GPA) versions 2017 and 2022 stratified patients with different OS; patients with higher GPA index scores had significantly longer OS (p = 0.0368 and 0.0407 for version 2017 and 2022, respectively).