260 - Consolidative Stereotactic Radiotherapy in Metastatic EGFR-Mutant Non-Small Cell Lung Cancer Receiving First-Line Third-Generation EGFR Tyrosine Kinase Inhibitors: A Prospective Phase II Trial

Y. Zhou¹, J. Ni², and Z. Zhu³; ¹Shanghai Medical College, Fudan University, Shanghai, China, ²Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China, ³Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China

Purpose/Objective(s): To evaluate the efficacy and safety of consolidative stereotactic radiotherapy (SRT) in patients with EGFR-mutant NSCLC who developed oligo-residual disease after first-line third-generation EGFR tyrosine kinase inhibitors (TKIs). Materials/

Methods: A single-arm, phase II trial was conducted in patients with EGFR-mutant NSCLC who received SRT for oligo-residual disease after first-line third-generation EGFR TKIs. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and toxicity graded using CTCAE. A propensity score-matched comparison was also conducted with a contemporary cohort of patients who received EGFR TKIs alone.
Results: Sixty-four patients were enrolled in the trial. With a median follow-up of 18.2 (IQR, 13.6-26.4) months, the median PFS in all patients was 29.9 (95%CI, 21.0-38.8) months, with the lower boundary exceeding the predefined threshold. The median OS time had not been reached (95%CI, NA) and the 2-year OS rate was 88.8% (95%CI 70.3%-96.0%). In patients with cranial oligo-residual disease and receiving cranial SRT, the median PFS was 27.0 (95%CI, 8.2-45.8) months. Adverse events (AE) were manageable, with pneumonitis and esophagitis being the most common toxicities. Four patients (6.3%) reported grade =3 AEs, each for pneumonitis, esophagitis, leukopenia and radiation necrosis. Propensity score-matched analysis showed significantly prolonged PFS in the SRT+TKI group compared to the TKI alone group (HR 0.45, 95%CI 0.25-0.79; p =0.005).
Conclusion: Consolidative SRT in patients with oligo-residual disease after first-line third-generation EGFR TKIs showed promising efficacy and acceptable toxicity profiles. This treatment approach may delay acquired resistance and improve survival outcomes. Further validation in larger prospective studies is warranted.