2504 - Optimal Intervention Timing for Craniocerebral Radiotherapy in Patients with EGFR-Mutant Lung Adenocarcinoma and Brain Metastases

G. Deng¹, and Z. Li²; ¹Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences,, Jinan, China, ²SHANDONG CANCER HOSPITAL AND INSTITUTE, JINAN, China

Purpose/Objective(s): We evaluated the efficacy of intervention timing of craniocerebral radiotherapy (RT) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) on prognosis of patients with EGFR mutant lung adenocarcinoma complicated with brain metastasis. Materials/

Methods: In total, 670 patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations were enrolled in this retrospective study. Propensity score matching (PSM) was conducted to adjust for demographic and clinical covariates and to compare survival differences between the EGFR-TKI plus craniocerebral RT group and the EGFR-TKI only group. Patients were divided into two groups according to timing of craniocerebral RT interventions.
Results: For 603 patients after excluded patients who received third-generation EGFR-TKIs in the first-line setting, the median overall survival (OS) was 48.8months, and the median intracranial progression-free survival (iPFS) was 14.2 months before PSM. After PSM, the median OS of EGFR-TKIs+craniocerebral RT group and EGFR-TKI only group was 52.0 months and 43.2 months, respectively (p=0.0363). Of 417 patients who underwent craniocerebral RT, were enrolled subsequently and divided into groups A (Lung-molGPA 1-2) and B (Lung-molGPA 2.5-4) according to the lung-molGPA score. For group A, the median OS of upfront-group and delay-group was 27 and 42.1 months, respectively (p = 0.0019). For patients in group B, there was no significant difference in OS between the two groups (p = 0.9642). The 348 patients enrolled who used the third generation of EGFR-TKIs during the treatment. the median OS was 61.4months, while the median iPFS was 15.0months before PSM. After PSM, the median OS of EGFR-TKIs+craniocerebral radiotherapy group and EGFR-TKI alone group was 68.1 months and 48.4 months respectively (p= 0.0178). Of 206 patients who underwent craniocerebral RT, were enrolled subsequently and divided into upfront-group and delay-group showed that the median OS was 78.7 and 67.7 months respectively (p =0.2439). For group A, the median OS of upfront-group and delay-group was 27.9 and 45.3 months, respectively (p = 0.0072). For patients in group B, there was significant difference in OS between the two groups (p = 0.0379). The median OS of the two groups was 110.0 and 70.5 months, respectively.
Conclusion: For patients with craniocerebral metastases of EGFR-mutant lung adenocarcinoma, combination of EGFR-TKIs and craniocerebral RT confers enhanced survival benefits. In patients with high Lung-molGPA scores, early administration of craniocerebral RT is recommended to improve both iPFS and OS.