133 - First-Line EGFR-TKIs Combined with Primary-Focus Radiotherapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC): A Real-World Retrospective Study

Purpose/Objective(s): This study aimed to observe the efficacy and safety of first-line EGFR-TKIs combined with primary tumor radiotherapy in advanced NSCLC in the real-world setting and to investigate the optimal timing of primary radiotherapy intervention.

Materials/Methods: A multicenter retrospective study was conducted to collect stage IV NSCLC patients treated with first/second-generation or third-generation EGFR-TKIs from 2017-05 to 2024-05. Enrolled patients received EGFR - TKI monotherapy (TKI group), primary-focus radiotherapy before EGFR - TKI resistance (TKI+RT group) or primary-focus radiotherapy after EGFR - TKI progression (TKI?RT group). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), mode of treatment failure and safety. Inverse probability of treatment weighting (IPTW) and multivariate Cox proportional hazards (CPH) regression were used for sensitivity analysis.

Results: A total of 211 first/second-generation EGFR-TKI-treated patients (91 in the TKI group, 45 in the TKI?RT group, and 75 in the TKI+RT group) and 131 third-generation EGFR-TKI-treated patients (50 in the TKI group, 31 in the TKI?RT group, and 50 in the TKI+RT group) were enrolled. The median PFS of 1st/2nd TKI group, 1st/2nd TKI?RT group, and 1st/2nd TKI+RT group were 11.9 months, 11.0 months, and 20.5 months, respectively. The median PFS of the 3rd TKI group, 3rd TKI?RT group, and 3rd TKI + RT group was 15.6 months, 15.0 months, and 40.5 months respectively. Regardless of the EGFR-TKI generation, patients in the TKI+RT group had a significantly longer PFS (P<0.01) and a significantly lower risk of primary site failure (P<0.01) compared with the TKI group and TKI?RT group. OS was significantly prolonged in the TKI+RT group compared with the TKI group (P<0.05). Both IPTW and CPH analyses confirmed the effectiveness of TKI+RT. One patient in each of the 1st/2nd TKI+RT group, 3rd TKI?RT group and 3rd TKI+RT group developed grade III radiation pneumonia, and there were no serious adverse effects leading to death.

Conclusion: For patients with EGFR-mutated advanced NSCLC, radiotherapy to the primary site prior to first-line EGFR-TKI resistance is a promising treatment strategy for prolonging PFS and OS with a tolerable safety profile.