Local cranial radiation combined with third-generation tyrosine kinase inhibitors improve leptomeningeal metastasis disease-free survival in patients with EGFR-mutated non-small cell lung cancer and brain metastasis.

PURPOSE: The role of local cranial radiation (LCR) combined with third-generation tyrosine kinase inhibitors (TKIs) in the following the progression to leptomeningeal metastasis (LM) in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with brain metastasis (BM) remains unclear. This study investigates whether LCR combined with third-generation TKIs can influence the occurrence LM in EGFR-mutated NSCLC with BM.

METHODS: Patients diagnosed with EGFR exon 19del or exon 21 L858R mutant NSCLC with LM in Guangdong Sanjiu Brain Hospital were recruited into the study between January 1, 2018 and December 31, 2023. They were separated into two groups according to whether they received LCR during the period from BM to LM on not. The primary endpoints were the LM disease-free survival (LM-DFS) and LM rate.

RESULTS: A total of 93 patients were enrolled, 60 in the TKIs group and 33 in the LCR + TKIs group. The median LM-DFS of the TKIs group and the LCR + TKIs group were 14.1 months (95% CI 12.3-19.8 months) and 27.0 months (95% CI 19.4-35.1 months), respectively (p < 0.01). After propensity score matching, the median LM-DFS were 13.2 months (95% CI 9.5-21.6 months) and 24.6 months (95% CI 18.1-35.1 months), respectively (p = 0.01). 2-year LM rates in TKIs group and LCR + TKIs group were 78.3% and 45.5% in all patients (p < 0.01); 76.9% and 50.0% in matched cohort (p = 0.02), respectively.

CONCLUSION: LCR combined with third-generation TKIs could improve LM-DFS and decrease 2-year LM rate compared with third-generation TKIs alone. Further studies are required to ascertain this effect.