First-line treatment with TKI plus brain radiotherapy versus TKI alone in EGFR-mutated non-small cell Lung cancer with brain metastases: a systematic review and meta-analysis

Abstract

Background It remains uncertain whether first-line treatment with upfront brain radiotherapy (RT) in combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is superior to EGFR-TKIs alone for EGFR-mutated non-small cell lung cancer with newly diagnosed brain metastases (BMs). Therefore, we performed a meta-analysis to address this issue. Methods We searched PubMed, Embase, Cochrane Library, and Web of Science databases for eligible studies published until February 28, 2023. The primary outcomes of interest were overall survival (OS) and intracranial progression-free survival (iPFS), reported as hazard ratios (HRs) and 95% confidence intervals (CIs). Results Twenty-four retrospective studies with 3184 patients were included. First- or second-generation EGFR-TKIs were used in each study. Upfront brain RT plus EGFR-TKIs significantly prolonged OS (HR = 0.75, 95% CI: 0.64–0.88) and iPFS (HR = 0.61, 95% CI: 0.52–0.72) compared to EGFR-TKIs alone. There were no significant differences in OS and iPFS benefits from the combination therapy between asymptomatic and symptomatic patients, patients with exon 19 and 21 mutations, patients with 1–3 and > 3 BMs, and males and females, respectively (HRs interaction, P > 0.05 for each subgroup comparison). Conclusions First-line treatment with upfront brain RT plus EGFR-TKIs is likely to be more effective than EGFR-TKIs alone. The benefits of combination therapy did not appear to be significantly affected by BM-related symptoms, EGFR mutation subtype, number of BMs, or sex.

Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT

“…Additionally, in the subgroup of patients with the L858R mutation, the OS was significantly longer in the osimertinib plus upfront radiotherapy group compared to the osimertinib alone group (Zhai et al 2021 ). A meta-analysis of 24 studies that examined the effectiveness of combining upfront brain radiation therapy (RT) with first-/second-generation EGFR-TKIs compared to using only first-/second-generation EGFR-TKIs (Song et al 2023 ). The meta-analysis revealed that there was no significant discrepancy in the benefit of iPFS between the two groups, encompassing both asymptomatic and symptomatic patients.…”

Distinct Progression and Efficacy of First-Line Osimertinib Treatment According to Mutation Subtypes in Metastatic NSCLC Harboring EGFR Mutations

“… 37 Indeed, previous reports revealed that combination therapy with radiotherapy and EGFR TKI was associated with better outcomes than those achieved with TKI alone in EGFR mutation-positive NSCLC with brain metastases. 38 , 39 The biological rationale for differences in CNS metastasis development between 19del and L858R remains unclear owing to the limited insight into the genetic makeup of metastasis. The variation in resistance mutations and differences in co-occurring mutations may define the risk of CNS metastasis progression.…”