Early stereotactic body radiation therapy improves progression-free survival of first-generation EGFR tyrosine kinase inhibitors in EGFR-mutated lung cancer: an observational cohort study

Background: Stereotactic body radiation therapy (SBRT) in treating non-small-cell lung cancer (NSCLC) exhibits a remarkable therapeutic efficacy. However, its effectiveness in overcoming resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced EGFR mutations (EGFRm) NSCLC remains uncertain.

Objective: We aimed to analyze the effect of SBRT on patients with first-line EGFR-TKIs.

Design and methods: Eligible patients with advanced NSCLC initially diagnosed with EGFRm were enrolled. Patients in the EGFR-TKIs group received only the first-generation EGFR-TKIs until disease progression or death, while the others in the EGFR-TKIs + SBRT group received EGFR-TKIs and early SBRT (dose of 40-60 Gy/5-8 F) targeting the primary lung tumor at 1 month after EGFR-TKIs. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were treatment-related adverse effects, overall survival (OS), and sites of initial failure.

Results: A total of 184 advanced NSCLC patients with EGFRm were enrolled, including 39 patients in the EGFR-TKIs + SBRT group and 145 patients in the EGFR-TKIs group. The median PFS was 15.50 months in the EGFR-TKIs + SBRT group compared to 9.33 months in the EGFR-TKIs group (p = 0.0020). However, the median OS was 29.10 months in the EGFR-TKIs + SBRT group and 26.33 months in the EGFR-TKIs group, with no significant difference observed (p = 0.22). SBRT is an independent positive prognostic factor for PFS in advanced EGFRm NSCLC. EGFR exon 19 deletion mutation (16.33 vs 11.55 months, p = 0.0087) and fewer metastases (0-5) (31.94 vs 9.59 months, p = 0.0059) were associated with improved PFS in EGFR-TKIs + SBRT versus EGFR-TKIs. Combination therapy increased radiation pneumonitis mainly in Grades 1-2 (89.74% vs 0.0%). The EGFR-TKIs + SBRT group mainly had new site failure (57.10% vs 32.10%) rather than the original site failure.

Conclusion: Early SBRT for primary lung tumors may overcome targeted resistance in advanced EGFRm NSCLC patients combined with EGFR-TKIs without serious toxicities, especially for EGFR exon 19-del.

Trial registration: ChiCTR-OIN-17013920.