ArticleBritish journal of cancer2026
Furmonertinib combined with bevacizumab in EGFR-TKI-resistant leptomeningeal metastasis: analysis of the CSF ctDNA molecular response and survival outcomes.
Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Abstract
backgroundLeptomeningeal metastasis (LM) after the development of third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance is indicative of a poor prognosis in EGFR-mutant non-small cell lung cancer (NSCLC), and no standardised treatments are currently available. The aims of this study were to evaluate the outcomes of combination therapy with bevacizumab plus high-dose furmonertinib in this setting and to assess the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) molecular response as a treatment response biomarker.
methodsThis real-world study included 104 patients with EGFR-mutant NSCLC who experienced LM progression after treatment with third-generation TKIs. Cohort 1 (n = 62) received combination therapy with furmonertinib (160 mg) + bevacizumab, and Cohort 2 (n = 42) received furmonertinib (160 mg) monotherapy. The primary endpoints were intracranial progression-free survival (iPFS) and overall survival (OS). In the longitudinal CSF ctDNA analysis, a molecular response was defined as follows: ΔctDNA ≤ 0.8 × baseline.
resultsCombination therapy with bevacizumab plus high-dose furmonertinib significantly improved the LM response compared to that of furmonertinib monotherapy (median iPFS: 6.77 vs 4.04 months, respectively, 95% CI: 0.41-0.98, p = 0.038; median OS: 15.31 vs 7.10 months, respectively, 95% CI: 0.29-0.82, p = 0.002). The CSF ctDNA analysis revealed that 31/47 patients (66%) achieved a molecular response; those that did experienced significantly prolonged survival outcomes compared to those of patients who did not (iPFS: 8.94 vs 6.67 months, respectively (HR = 0.40, 95% CI: 0.21-0.79); OS: 20.44 vs 8.71 months, respectively (HR = 0.34, 95% CI: 0.14-0.83)). A longitudinal decline in ctDNA across two time points further correlated with survival benefits (iPFS: 9.96 vs 7.33 months (HR = 0.42, p = 0.01); OS: 25.63 vs.15.31 months, (HR = 0.28, p = 0.03)).
conclusionBevacizumab synergises with high-dose furmonertinib to significantly improve survival outcomes in TKI-resistant LM. A positive CSF ctDNA molecular response (ΔctDNA ≤ 0.8 × baseline) is predictive of clinical benefits, supporting its utility for real-time monitoring. This combination therapy represents a promising strategy for the treatment of a population with unmet needs.
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