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Efficacy and Safety of Immune Checkpoint Inhibitors for Advanced Non-small Cell Lung Cancer with Leptomeningeal Metastases Harboring Targetable Mutations

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Date 2024 Aug 9
PMID 39118876
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Abstract

Background: Driver gene-positive non-small cell lung cancer (NSCLC) patients are prone to develop leptomeningeal metastasis (LM), leading to an extremely high mortality. The objective of this study was to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) treatments for patients with NSCLC and LM harboring targetable mutations.

Methods: We retrospectively collected records of patients with NSCLC harboring targetable mutations and prescribed ICIs following the diagnosis of LM at Huashan Hospital, Fudan University. In addition, we reviewed relevant literature and enrolled patients who met the inclusion criteria. Clinical characteristics were statistically analyzed, and the Kaplan-Meier method and log-rank test were employed to assess the median progression-free survival (mPFS) and median overall survival (mOS).

Results: A total of 37 patients with NSCLC harboring targetable mutations who received ICIs after LM diagnosis were included. The median age of the enrolled patients was 54 years (range, 33-70 years), and 62.2% were female. Following ICI administration, the intracranial objective response rate (iORR) and intracranial disease control rate (iDCR) for all enrolled patients were 18.9% and 62.2%, respectively. The mPFS of all patients was 2.5 months [95% confidence interval (CI): 2.166-2.834 months] and the mOS was 5.8 months (95% CI: 5.087-6.513 months). Both univariate and multivariate analyses revealed a significant increase in mOS or individuals who had previously undergone cranial radiation therapy compared to those who had not. Furthermore, different histology molecular types were found to be potentially associated with survival time.

Conclusions: Some patients with NSCLC harboring targetable gene mutations following LM diagnosis may benefit from ICI treatment with relatively good tolerance. However, further screening of the most suitable patient populations for ICIs is required.

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