Upfront Radiation Therapy with TKI Improved the Intracranial PFS but Not OS in the NSCLC Patients Harboring EGFR Mutation and Brain Metastases

Abstract

Patients with epidermal growth factor receptor (EGFR) mutation have a 50-70% risk for developing brain metastasis (BM) in non-small cell lung cancer (NSCLC). The tyrosine kinase inhibitors (TKI) have more than 70% intracranial response rate, which challenge the role of upfront intracranial radiation therapy (RT) in BM. Therefore, we conducted a retrospective analysis to demonstrate the value of adding upfront RT to TKI in the treatment. We retrospectively reviewed the patients treated in our institution from 2010 to 2016. Patients had histologically confirmed NSCLC, EGFR mutation, CT or MRI confirmed brain metastases, treated with TKI or upfront RT concurrent with/followed by TKI, were included in this study. Of note, patients had TKI use before brain metastases were excluded. Intracranial progression-free survival (iPFS) was estimated using a competing risks model. Kaplan-Meier analysis was used to analyses iPFS, outcranial PFS (ePFS) and overall survival (OS) and long-rank test was used to compare the data. Among the 93 patients who meet the inclusion criteria, 53 patients received upfront RT while 40 patients received TKI only. The baseline of two groups, including stage at diagnosis, GPA score, symptom from brain metastasis, extracranial metastases, are balanced. The median iPFS for upfront RT and TKI was 27.6 months (95% CI 20.2 to 35.0) and 16.1 months (95%CI 14.6 to17.6), respectively (log-rank p=0.053). Using a competing risks regression model, upfront RT group showed lower intracranial progression after controlling for confounding factors, with adjusted subdistribution hazard ratios of 0.34 (95% CI, 0.17 to 0.67; p = 0.002). There was no difference in the median ePFS time. The number of patients who experience extracranial failure as first site of progression was 26 (49.1%) and 21 (52.5%) in up-front RT and TKI group, respectively. The median OS for upfront RT and TKI was 35.4 months (95% CI 30.3 to 40.6) and 35.8 months (95%CI 27.1 to 44.5), respectively (log-rank p=0.695). After the Cox proportional hazards analysis, only the Osimertinib usage (HR 0.27, 95%CI 0.10 to 0.77) was a protective factor to OS. Upfront RT prolonged the iPFS of the patients but not the OS. Whether upfront RT is the optimal choice for EGFR mutant NSCLC patients with BM still need the evidence from prospect clinical trials.