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Meta-Analysis
. 2024 Oct 2;14(1):22901.
doi: 10.1038/s41598-024-74496-0.

First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis

Jietao Ma  1   2 , Xiaoxue Pang  1   2 , Shuling Zhang  1   2 , Letian Huang  1   2 , Li Sun  1   2 , Chengbo Han  3   4   5
Affiliations
Meta-Analysis

First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis

Jietao Ma et al. Sci Rep. .

Abstract

This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433-0.973) and 0.682 (95% CI: 0.464-0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511-1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14-3.4) and PFS 2.13 (95% CI: 1.28-3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.

Keywords: Brain metastases; EGFR-TKIs; First-line therapy; Non-small cell lung cancer; Overall survival.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA diagram of search results and selections.
Fig. 2
Fig. 2
Network meta-analysis plots comparing therapies for (A) overall survival (OS), (B) progression-free survival (PFS), (C) intracranial PFS (iPFS), (D) intracranial objective response rate (iORR), and (E) intracranial disease control rate (iDCR) in EGFR-mutant NSCLC with brain metastases. Lines indicate individual head-to-head comparisons, with line thickness indicating the number of trials per comparison.
Fig. 3
Fig. 3
Rankograms of cumulative efficacy probabilities for (A) overall survival (OS), (B) progression-free survival (PFS), (C) intracranial progression-free survival (iPFS), (D) intracranial objective response rate (iORR), and (E) intracranial disease control rate (iDCR) in EGFR-mutant NSCLC with brain metastases, ordered from highest to lowest probability from top to bottom.
Fig. 4
Fig. 4
Risk of bias assessment (A) in individual studies and (B) across the included studies.
Fig. 5
Fig. 5
Assessment of publication bias by funnel plots for (A) overall survival (OS), (B) progression-free survival (PFS), (C) intracranial progression-free survival (iPFS), (D) intracranial objective response rate (iORR), and (E) intracranial disease control rate (iDCR).
See this image and copyright information in PMC

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