Multiple treatment modalities for brain metastasis in patients with EGFR-mutant non-small-cell lung cancer

Background: There are many controversies concerning the best management of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients with brain metastases (BMs). The use of upfront EGFR tyrosine kinase inhibitors (TKIs) and the with-holding of local therapies or upfront radiation therapies (RTs) remain controversial. Available treatment options include local therapies such as whole-brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) and surgery, EGFR-TKIs, and chemotherapy. However, the optimal management of combination therapies is still under consideration. Patients and methods: A total of 45 EGFR-mutated NSCLC patients with BMs were included. All patients successively received EGFR-TKIs, RT (WBRT or SRS), and chemotherapy between 2010 and 2015 at Zhejiang Cancer Hospital. Patient follow-up was conducted by telephone until February 2017. The treatment response was evaluated, and survival data were collected and analyzed by Kaplan-Meier analysis and the Cox regression method. Results: The median overall survival (OS) was 28 months. Patients with the exon 19 deletion showed the strongest trend toward a longer median OS compared to patients with the exon 21 L858R mutation (not reached vs 26.5 months, P=0.0969). There was no difference in OS between the upfront RT group and the deferral group (26.5 vs 28 months, P=0.57), and similar results were found between the first-line chemotherapy group and the EGFR-TKI group (28 vs 23.2 months, P=0.499). In multivariate analysis, the prognosis correlated with EGFR mutation type (P=0.017). Conclusion: EGFR-mutant NSCLC patients with BM benefited from the combination and sequential therapies of EGFR-TKIs, chemotherapy, and RTs. Patients with the EGFR exon 19 deletion may have a better OS. However, the optimal timing of RT interval remains to be explored.