EGFR-TKIs with or without Stereotactic Body Radiotherapy to Primary Lesion in the Advanced EGFR-Mutated Non- Small Cell Lung Cancer

Abstract Background: Advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations presents a clinical challenge due to eventual resistance to EGFR tyrosine kinase inhibitors (TKIs). This study aimed to evaluate the efficacy and safety of combining EGFR-TKI therapy with stereotactic body radiotherapy (SBRT) to primary lesions in treating EGFR-mutant NSCLC patients. Methods: A retrospective analysis was conducted on 58 EGFR-mutant NSCLC patients treated between 2018 and 2023. Patients were divided into two groups: EGFR-TKI alone (n=43) and EGFR-TKI combined with SBRT (n=15). Clinical outcomes were assessed, including progression-free survival (PFS), overall survival (OS), and treatment-related toxicities. Statistical analyses were performed to compare the effectiveness of the treatment modalities. Results: A total of 485 patients with advanced NSCLC were screened, and 58 patients were eligible for enrollment in this study. Of the 58 eligible patients, 15 (25.9%) received EGFR-TKI treatment alone and 43(74.1%) received EGFR-TKI treatment plus with SBRT to lung primary tumor. The TKIs plus SBRT group exhibited a significant extension in PFS compared to the TKIs alone group (not reached vs 10.2 months, p < 0.001). Multivariate analysis identified SBRT as the sole significant positive predictor for PFS. Adverse event profiles were comparable between groups, with manageable toxicities and no Grade 4-5 events reported. Meta-analysis revealed that combined TKI and SBRT treatment significantly improved PFS (HR 0.39, 95% CI 0.24-0.64, P < 0.001) but showed no significant OS benefit. After excluding retrospective studies, a significant OS benefit was observed. (HR 0.47, 95% CI 0.33-0.69, P < 0.001). No increased incidence of grade ≥3 AEs with SBRT was observed, but the TKIs plus SBRT group had higher probabilities of pneumonitis and radiation dermatitis than the TKIs alone group. Conclusions: Our study suggests that the addition of SBRT to EGFR-TKI therapy significantly extends PFS and OS in EGFR-mutant NSCLC patients. The results emphasize the potential of combining local radiotherapy with targeted therapy, offering a promising approach to improve outcomes in this patient population.