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Immunotherapy and next-generation TKIs: From second to frontline treatment (ID 55)
- Event: ELCC 2018
- Type: Poster Discussion session
- Presentations: 1
- Moderators:P. Garrido Lopez, S. Ekman, S. Ortiz-Cuaran, E. Wauters
- Coordinates: 4/12/2018, 07:45 - 09:00, Room A
142PD - Detection of EGFR mutations in cerebrospinal fluid of EGFR-mutant lung adenocarcinoma with brain metastases (ID 491)
07:45 - 09:00 | Author(s): W. Wu
A large proportion of lung adenocarcinoma (LADC) with epidermal growth factor receptor (EGFR) activating mutation will develop brain metastases (BMs) throughout the course of their disease. BM lesions were hard to obtain, which resulted in poor understanding of resistance mechanisms of EGFR tyrosine kinase inhibitors (EGFR-TKIs) therapy in these patients. Liquid biopsy of cerebrospinal fluid (CSF) may provide potential information of intracranial lesions. Herein, we aimed to investigate the alternative detection of EGFR mutation status in CSF.
Between July 2014 and June 2017 in Beijing Chest Hospital, thirty LADC patients with BMs carrying activating EGFR mutation in their primary tumors determined by amplification-refractory mutation system (ARMS) assay were enrolled. Their matched CSF and plasma samples were collected. Droplet digital PCR assays (ddPCR) for EGFR mutations, including 19del, L858R, and T790M were developed using two millilitres CSF or plasma. The clinical response of intracranial objective response rate (iRR), intracranial progression-free survival (iPFS), and intracranial overall survival (iOS) from the time of diagnosis of BM were evaluated.
All of the included patients were Chinese and had been diagnosed with stage IV lung adenocarcinoma. Out of 30 patients, 21 were females and 9 males aged from 34 to 75 years old (median age of 58 years old). The majority (24/30) classified as good Eastern Cooperative Oncology Goup performance status (ECOG PS <2). In all of cases, CSF cytology were negative and examinations of cranial imaging showed no leptomeningeal metastases (LM). In ddPCR assays, EGFR mutations were detected in CSF of 10 patients (33.3%), including three cases with EGFR T790M mutations, and in plasma of 14 patients (46.7%), including six cases with EGFR T790M mutations. All EGFR T790M mutations were found during or after EGFR-TKIs treatments. Five patients with activating EGFR mutations in CSF achieved intracranial partial response (iPR) after treated with combination of first-generation EGFR-TKIs and whole brain radiotherapy (WBRT)/stereotactic radiosurgery (SRS). Three patients with EGFR T790M mutations in CSF achieved iPR after treated with second-line osimertinib. The median iOS and iPFS from the time of diagnosis of BM were 15.0 months and 11.0 months, respectively. The following Table shows the EGFR testing result in detail.Table: (Abstract 142PD)EGFR testing result
Patient Primary Tissue EGFR Mutation(ARMS) CSF EGFR Mutation Plasma EGFR Mutation Status Frequency Status Frequency 1 19del WT T790M 0.3% 2 19del WT 19del 3 L858R L858R 37.9% L858R 2.0% 4 L858R WT WT 5 19del WT WT 6 L858R WT L858R/T790M 10.8%/26.5% 7 L858R WT WT 8 19del 19del 69.7% 19del/T790M 11.0%/7.0% 9 L858R WT WT 10 19del WT WT 11 19del WT WT 12 L858R WT L858R/T790M 2.4%/0.2% 13 L858R L858R 32.8% WT 14 19del WT WT 15 19del 19del/T790M 13.2%/0.5% 19del/T790M 14.4%/3.5% 16 L858R WT WT 17 L858R L858R/T790M 16.2%/2.0% L858R/T790M 8.1%/2.2% 18 L858R WT WT 19 19del 19del 43.3% 19del 14.9% 20 19del WT WT 21 19del WT 19del 3.7% 22 19del 19del 21.8% 19del 7.4% 23 L858R WT L858R 20.5% 24 19del WT 19del 11.4% 25 19del WT WT 26 19del WT 19del 0.8% 27 L858R L858R 7.2% L858R 5.2% 28 19del 19del 6.9% WT 29 19del 19del/T790M 35.7%/12.1% WT 30 19del WT 19del 15.3%
It was feasible to test EGFR mutation in CSF and plasma. CSF may serve as liquid biopsy of advanced LADC with BMs by detecting cfDNA within CSF to characterize EGFR mutations. For those advanced LADC with BMs harboring EGFR mutation, dynamic monitoring EGFR mutation status of CSF would be an appropriate choice.
Clinical trial identification:
Legal entity responsible for the study:
Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Beijing Municipal Administration of Hospitals Youth Talent Training Project (Grant No. QML20151502)
All authors have declared no conflicts of interest.
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