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Background <p>In patients with EGFR-mutant non–small cell lung cancer (NSCLC), leptomeningeal metastasis (LM) following progression on third-generation EGFR tyrosine kinase inhibitors (TKIs) remains a life-threatening complication.</p> Methods <p>In this ambispective cohort study, we included 21 patients with LM who progressed after third-generation EGFR-TKI therapy and subsequently received salvage treatment with dacomitinib combined with intraventricular chemotherapy (IVC) via an Ommaya reservoir. The primary outcome was intracranial progression-free survival (iPFS); secondary outcomes included intracranial disease control rate (iDCR), intracranial objective response rate (iORR), overall survival (OS), and safety.</p> Results <p>According to RANO-LM criteria, the median iPFS was 4.44 months, the iDCR was 81.0% (17/21), and the iORR was 19.0% (4/21). Patients harboring uncommon or compound EGFR mutations (<i>n</i> = 11) demonstrated longer median iPFS compared with those carrying L858R or exon 19 deletions (7.98 vs. 3.12 months). The 6-month OS rate was 78.1%. Improvements in performance status, neurological examination findings, and clinical symptoms were observed in 42.9%, 57.1%, and 71.4% of patients, respectively. The regimen was tolerable; the most common adverse events were diarrhea (61.9%, including one grade 3 event) and neutropenia (52.4%, with 19.0% grade ≥ 3), and no treatment-related deaths occurred.</p> Conclusion <p>These findings suggest that dacomitinib combined with IVC may represent a feasible salvage therapy for TKI-resistant LM in patients with NSCLC, with potentially enhanced benefits in those with uncommon or compound EGFR genotypes.</p>

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Salvage dacomitinib plus intraventricular pemetrexed for leptomeningeal metastasis after failure of third‑generation EGFR‑TKIs in EGFR‑mutant NSCLC: an ambispective cohort study

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Xiaoyue Wang,
  • Hua Wen,
  • Yuwen Xie,
  • Ting Xu,
  • Hehui Fang,
  • Na Liu,
  • Shencun Fang

摘要

Background

In patients with EGFR-mutant non–small cell lung cancer (NSCLC), leptomeningeal metastasis (LM) following progression on third-generation EGFR tyrosine kinase inhibitors (TKIs) remains a life-threatening complication.

Methods

In this ambispective cohort study, we included 21 patients with LM who progressed after third-generation EGFR-TKI therapy and subsequently received salvage treatment with dacomitinib combined with intraventricular chemotherapy (IVC) via an Ommaya reservoir. The primary outcome was intracranial progression-free survival (iPFS); secondary outcomes included intracranial disease control rate (iDCR), intracranial objective response rate (iORR), overall survival (OS), and safety.

Results

According to RANO-LM criteria, the median iPFS was 4.44 months, the iDCR was 81.0% (17/21), and the iORR was 19.0% (4/21). Patients harboring uncommon or compound EGFR mutations (n = 11) demonstrated longer median iPFS compared with those carrying L858R or exon 19 deletions (7.98 vs. 3.12 months). The 6-month OS rate was 78.1%. Improvements in performance status, neurological examination findings, and clinical symptoms were observed in 42.9%, 57.1%, and 71.4% of patients, respectively. The regimen was tolerable; the most common adverse events were diarrhea (61.9%, including one grade 3 event) and neutropenia (52.4%, with 19.0% grade ≥ 3), and no treatment-related deaths occurred.

Conclusion

These findings suggest that dacomitinib combined with IVC may represent a feasible salvage therapy for TKI-resistant LM in patients with NSCLC, with potentially enhanced benefits in those with uncommon or compound EGFR genotypes.