Efficacy of brain radiotherapy plus EGFR-TKI for EGFR-mutated non-small cell lung cancer patients who develop brain metastasis.

Introduction: To analyze the appropriate treatment methods or timing to use epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and brain radiation treatment (RT) for symptomatic and asymptomatic brain metastases (BM) in patients with EGFR mutation non-small cell lung cancer (NSCLC).

Material and methods: We retrospectively studied patients diagnosed with EGFR gene mutated NSCLC who developed brain metastasis between June 2006 and December 2015 at Zhejiang Cancer Hospital. Treatment data were assessed in 181 patients with 49 symptomatic BM and 132 asymptomatic BM retrospectively.

Results: In 49 symptomatic BM patients, the median OS of the stereotactic radiosurgery (SRS)-treated group was longer than in the whole brain radiotherapy (WBRT) group (37.7 vs. 21.1 months) ( p = 0.194). In the group of 132 asymptomatic brain metastasis patients, the median overall survival (mOS) was longer in upfront brain radiotherapy compared with the upfront TKI group (24.9 vs. 17.4 months) ( p = 0.035). In further analysis regarding the timing of using radiotherapy, out of all 74 patients, 33 underwent concurrent TKI and brain radiation, 13 received TKI after first-line RT treatment and 28 patients received radiotherapy after TKI failure. The intracranial progression free survival (iPFS) of the three groups was 11.1 months, 11.3 months and 8.1 months ( p = 0.032), respectively. The mOS of the three groups was 21.9 months, 26.2 months and 17.1 months, respectively ( p = 0.085).

Conclusions: Our research indicated that delayed brain RT may result in inferior iPFS in EGFR mutated NSCLC patients with asymptomatic brain metastases, but no OS benefit was obtained. In addition, our study revealed that patients treated with SRS had a significantly longer OS for symptomatic BM. Future prospective study of the optimal management strategy with WBRT or SRS and TKI for this patient cohort is urgently needed.