Osimertinib Improves Overall Survival in Patients with Leptomeningeal Metastases Associated with EGFR-Mutated Non-Small-Cell Lung Cancer Regardless of Cerebrospinal Fluid T790M Mutational Status.

Milan Zhang,Wei Li,Jiewen Zhang,Weifeng Ma,Lingzhi Qin,Yushu Jiang,Huiqin Liu

doi:10.1155/2021/6968194

Abstract

Osimertinib has demonstrated promising efficacy against leptomeningeal metastasis (LM) associated with T790M-positive non-small-cell lung cancer (NSCLC). However, the effect of cerebrospinal fluid's (CSF's) epidermal growth factor receptor (EGFR) T790M mutation on osimertinib efficacy remains unclear.Seventy-eight patients were studied with EGFR-mutated NSCLC and LM. Case data were collected and EGFR mutation status of circulating cell-free DNA from paired CSF, and plasma of 23 patients with LM was detected using droplet digital PCR. The median overall survival (mOS) was 8.08 months (95% CI: 6.07–10.09) in the study. Forty-four osimertinib-treated patients had an improved mOS of 13.15 (95% CI: 5.74–20.57) and a median progression-free survival (PFS) of 9.50 months (95% CI: 6.77–12.23) when compared with patients treated with first- or second-generation EGFR-TKI (mOS = 3.00 months (95% CI: 1.32–4.68) and median PFS = 1.50 months (95% CI: 0.00–3.14)). In the osimertinib group, mOS values for CSF with and without T790M mutation were 22.15 months (95% CI: 9.44–34.87) and 13.39 months (95% CI: 7.01–19.76), respectively, with no statistical differences. Regardless of the CSF T790M mutation status, osimertinib demonstrated significant efficacy against LM associated with NSCLC.

Highlights

Leptomeningeal metastasis (LM) is defined as the spread of malignant cells within the leptomeninges and subarachnoid space, resulting in a devastating prognosis with limited treatment options [1]
Twenty-five patients with Non-small-cell lung cancer (NSCLC) presented with LM at initial diagnosis. e median time from NSCLC to LM diagnosis of the remaining 53 patients was 21 months
Forty-four osimertinib-treated patients had an improved median overall survival (mOS) of 13.15 months and a median progression-free survival (PFS) of

Summary

Introduction

Leptomeningeal metastasis (LM) is defined as the spread of malignant cells within the leptomeninges and subarachnoid space, resulting in a devastating prognosis with limited treatment options [1]. Non-small-cell lung cancer (NSCLC) is the most common primary tumor of LM, and epidermal growth factor receptor (EGFR) is the most important driver gene in NSCLC. EGFR mutations occur in 10–20% of Caucasian patients with NSCLC but in 40–60% of Asian patients [2]. E detection rate of LM in patients with NSCLC has been estimated to be 3–4% but 9–16% in patients with lung adenocarcinoma harboring EGFR mutations [3, 4]. EGFR mutation status is a critical prognostic factor in the treatment of NSCLC with LM. Circulating cell-free DNAs (cfDNAs) are extracellular nucleic acids released by tumor cells that can be useful biomarkers for early diagnosis and prognosis [5]. Because of the blood-brain barrier, the role of plasma cfDNA in the diagnosis of metastatic brain cancer is very limited. The enrichment of cerebrospinal fluid (CSF) with intracranial tumor cfDNA has become increasingly emphasized in intracranial tumor fluid biopsies [6, 7]

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