What question did this study set out to answer?

This research aims to determine the effectiveness of different EGFR-TKI treatment strategies in patients with NSCLC and brain metastases.

May 22, 2026Open Access

EGFR-TKI monotherapy versus combination therapy as first-line treatment for EGFR-mutant NSCLC with brain metastases: a real-world comparison analysis

Key Points

This research aims to determine the effectiveness of different EGFR-TKI treatment strategies in patients with NSCLC and brain metastases.
Retrospective analysis of 150 patients with EGFR-mutant NSCLC and brain metastases from 2019 to 2023.
Patients were grouped based on treatment: TKI alone, TKI + brain radiation, TKI + bevacizumab, TKI + chemotherapy.
Key metrics compared included intracranial progression-free survival, overall survival, and adverse events.
Median iPFS for TKI alone was 22.1 months, significantly lower than 32.9 months for TKI + BRT, and not reached for TKI + BEV and TKI + CT (p = 0.001).
TKI + BRT, TKI + BEV, and TKI + CT showed superior PFS and OS compared to TKI alone: OS for TKI alone was 40.1 months versus 67.1 months for TKI + BRT, and 79.8 months for TKI + CT (PFS, p = 0.014; OS, p = 0.015).
Addition of brain radiation or bevacizumab significantly reduced the risk of intracranial progression (HR = 0.375, p = 0.011; HR = 0.294, p = 0.001).

Abstract

Optimal first-line treatment for epidermal growth factor receptor (EGFR) mutant NSCLC with brain metastases (BMs) has not been fully defined. We aimed to compare different first-line tyrosine kinase inhibitor (TKI) combination therapies and monotherapy for these patients in a real-world setting, especially in the era of 3rd generation TKIs. Patients with EGFR-mutant NSCLC and BMs receiving first-line EGFR-TKIs from 2019 to 2023 were retrospectively reviewed (n = 150): TKI alone (n = 73), TKI plus brain radiation (TKI + BRT, n = 25), TKI plus bevacizumab (TKI + BEV, n = 38) and TKI plus chemotherapy (TKI + CT, n = 14). Intracranial progression-free survival (iPFS), PFS, overall survival (OS), responses and adverse events of each group were compared and survival beneficial population were explored. Among enrolled patients, majority (70.7%) received 3rd generation EGFR-TKIs and 29.3% received 1st /2nd generation drugs. The median iPFS of TKI alone group was significantly inferior than those in TKI + BRT, TKI + BEV and TKI + CT groups (22.1 vs. 32.9 months vs. not reached NR vs. NR, p = 0.001). The median PFS and OS were 11.1 and 40.1 months, 18.9 and 67.1 months, 16.5 and 38.8 months, 39.8 and 79.8 months, respectively, with TKI alone, TKI + BRT, TKI + BEV and TKI + CT (PFS, p = 0.014; OS, p = 0.015). The combination therapies brought iPFS and PFS benefits over TKI alone regardless of TKI generations. A linear correlation was demonstrated between iPFS and OS (R2 = 0.508, p < 0.001). Multivariate analysis revealed that the addition of BRT (HR = 0.375, 95%CI, 0.176–0.802, p = 0.011) or bevacizumab (HR = 0.294, 95%CI, 0.141–0.611, p = 0.001) significantly reduced intracranial progression risk. Whereas, the combinations of TKI and RT (HR = 0.326, 95%CI, 0.128–0.834, p = 0.019) or chemotherapy (HR = 0.083, 95%CI, 0.010–0.666, p = 0.019) were independent factors for favorable OS. No significant difference on survival or toxicity was observed among the three combination therapies. EGFR-TKI combination therapies improved iPFS, PFS and OS than TKI monotherapy for patients with EGFR-mutant NSCLC and BMs irrespective of TKI generation or combination strategy.

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Cite This Study

Qi et al. (Wed,) studied this question.

synapsesocial.com/papers/6a0ff38cd674f7c03778c3bf https://doi.org/https://doi.org/10.1186/s12885-026-16193-x

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