Survival benefit of thoracic radiotherapy plus EGFR-TKIs in patients with non-oligometastatic advanced non-small-cell lung cancer: a single-center retrospective study

Objectives: The study aims to evaluate the efficacy and safety of thoracic radiotherapy in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-treated patients with stage IV non-small-cell lung cancer (NSCLC). Methods: Patients with non-oligometastatic NSCLC harboring EGFR mutations were recruited. All patients received the first-generation TKI treatment with or without radiotherapy. The irradiated sites included primary and/or metastatic lesions. Of all the patients who underwent thoracic radiotherapy, some received radiotherapy before EGFR-TKI resistance, others received radiotherapy after progressive disease. Results: No statistically significant difference was observed in progression-free survival (PFS) (median 14.7 versus 11.2 months, p = 0.075) or overall survival (OS) (median 29.6 versus 40.6 months, p = 0.116) between patients treated with EGFR-TKIs alone and those with additional radiotherapy to any sites. However, EGFR inhibitors with thoracic radiation significantly improved OS (median 47.0 versus 31.0 months, p < 0.001) but not PFS (median 13.9 versus 11.9 months, p = 0.124). Moreover, longer PFS (median 18.3 versus 8.5 months, p < 0.001) was achieved in the preemptive thoracic radiation cohort than in the delayed thoracic radiation cohort. However, OS was similar between the two cohorts (median 40.6 versus 52.6 months, p = 0.124). The lower incidence rate of grade 1–2 pneumonitis occurred in preemptive radiation cohort (29.8% versus 75.8%, p < 0.001). Conclusion: Non-oligometastatic NSCLC patients with EGFR mutations benefited from thoracic radiotherapy while using EGFR inhibitors. Preemptive thoracic radiotherapy could be a competitive first-line therapeutic option due to superior PFS and favorable safety.