Primary Objective:
To evaluate the efficacy of high-dose firmonertinib combined with bevacizumab and intrathecal pemetrexed in EGFR Ex19del/L858R-mutated non-small cell lung cancer (NSCLC) with leptomeningeal metastasis (LM), as measured by Overall Survival (OS).
Secondary Objectives:
1. To assess the efficacy of this regimen in EGFR Ex20ins/PACC/L861Q-mutated NSCLC with LM.
2. To further evaluate therapeutic outcomes across cohorts, including:
* Time to Treatment Failure (TTF)
* Leptomeningeal Objective Response Rate (ORR-LM)
* Clinical Response Rate
3. To analyze the impact of this regimen on \*quality of life\* using standardized metrics:
* EORTC QLQ-C30
* EORTC QLQ-LC13
4. To assess safety profiles across cohorts, focusing on:
* Incidence and severity of adverse events (AEs) graded per \*CTCAE v5.0\*
* Frequency of treatment-related toxicities
Exploratory Objectives:
To investigate correlations between dynamic changes in:
* Plasma-derived circulating tumor DNA (ctDNA)
* Cerebrospinal fluid-derived cell-free DNA (cfDNA) and clinical outcomes through comparative analysis of genomic profiling and epigenetic signatures before and after treatment.