Abstract
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has intracranial activity in EGFR-mutant Non-Small Cell Lung Cancer (NSCLC). The optimal timing of brain radiotherapy (RT) and appropriate patients who need early brain RT remains undetermined. This is a retrospective study of EGFR-mutant NSCLC patients with newly diagnosed brain metastases (BMs) before EGFR-TKI initiation. Intra-cranial progression free survival (IC-PFS) and overall survival (OS) were measured from the date of EGFR-TKI treatment. A total of 113 patients were eligible, 49 received concurrent early brain RT with EGFR-TKI and 64 were treated with EGFR-TKI alone as initial therapy, including 27 with salvage RT upon BM progression. The patients with early brain RT had superior IC-PFS than those without early brain RT (21.4 vs 15.0 months, P=0.001), which remained significant in multivariate analysis (HR 0.30, P<0.001). The median overall survival (OS) for early RT, EGFR-TKI alone and salvage RT groups was 28.1, 24.5, and 24.6 months, respectively (P=0.604). Similar IC-PFS (23.6 vs 21.4 months, P=0.253) and OS (24.6 vs 28.1 months, P=0.385) were observed between salvage RT and early RT groups. For patients with Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) score of 0 to 2, early brain RT was the independent factor for improved OS (HR 0.33, P=0.025). In conclusion, concurrent early brain RT with EGFR-TKI may improve intracranial disease control in EGFR-mutant NSCLC with BM and have survival benefit in patients with low DS-GPA score. Salvage brain RT upon BM progression may be acceptable in some patients.
Highlights
Non-small cell lung cancer (NSCLC) is characterized by a high incidence of brain metastasis
This study demonstrated that patients treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) and early brain RT achieved a significantly longer Intracranial progression free survival (IC-PFS) than those initially treated with EGFRTKI alone on both univariate and multivariate analyses, with a median IC-PFS of 21.0 months and 15.0 months, respectively (P=0.001)
This is consistent with the literatures that reported by Naamit K and William J [6, 7], but patients in these two studies were not treated concurrently with brain RT and EGFR-TKI
Summary
Non-small cell lung cancer (NSCLC) is characterized by a high incidence of brain metastasis. 40% of patients diagnosed with NSCLC will develop brain metastasis (BM) during the course of their disease and this risk may be even higher in those with adenocarcinoma with epidermal growth factor receptor (EGFR) mutation [1, 2]. Several prospective studies have demonstrated that EGFR-TKIs alone show therapeutic benefits against BM for EGFR-mutant patients, with a response rate of up to 80%[10, 11]. The recently published multi-institutional analysis demonstrated that the use of upfront EGFR-TKI with deferral of radiotherapy is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases [14]. Other studies showed that addition of brain RT to EGFR-TKIs did not appear to have survival benefit compared to that of EGFRTKI treatment alone in EGFR-mutant NSCLC with BM [15, 16]. The management of EGFR mutated NSCLC patients with brain metastases is a significant clinical challenge and remains controversial
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