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W. Wu



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    JCES01 - Joint IASLC - Chinese Society for Clinical Oncology - Chinese Alliance Against Lung Cancer Session (ID 413)

    • Event: WCLC 2016
    • Type: Joint Chinese / English Session
    • Track:
    • Presentations: 1
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      JCES01.23 - EGFR Mutation Status Analysis in Cerebrospinal Fluid and Plasma of Advanced Lung Adenocarcinoma with Brain Metastases (ID 7065)

      W. Wu

      • Abstract
      • Slides

      Background:
      We aimed to investigate the feasibility of droplet digital PCR (ddPCR) for the detection of epidermal growth factor receptor (EGFR) mutations in circulating free DNA (cfDNA) from cerebrospinal fluid (CSF) and plasma of advanced Lung Adenocarcinoma (ADC) with brain metastases (BM).

      Methods:
      Fourteen advanced ADC patients with BM carrying activating EGFR mutations in tumour tissues were enrolled in this study, and their matched CSF and plasma samples were collected. EGFR mutations were detected by the Amplification Refractory Mutation System (ARMS) in tumour tissues. EGFR mutations, including 19del, L858R, and T790M were examined in cfDNA isolated from 2milliliter CSF or plasma by ddPCR assay. The clinical response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. Overall survival (OS) and progression free survival (PFS) after the diagnosis of BM were also evaluated.

      Results:
      Out of 14 patients, eleven were females and three males aged from 34 to 74 years old (median age of 55 years old). In all of cases, CSF cytology were negative. In ddPCR assays, EGFR mutations were detected in CSF of three patients (21.4%; one of 19del and two of L858R), and in plasma of six patients (42.9%; one of 19del, one of L858R, one of T790M, two of L858R&T790M, and one of 19del&T790M). All EGFR T790M mutations were found during or after EGFR-TKIs treatments. The three patients with activating EGFR mutations in CSF achieved partial response (PR) of BM after treated with combination of WBRT and EGFR-TKIs. The median OS and PFS after the diagnosis of BM were 18.0 months and 9.0 months, respectively.

      Patient Tissue EGFR CSF EGFR Plasma EGFR Systematic Treatment BM Treatment
      1 19del WT T790M Erotinib+Chemotherapy WBRT+Gamma knife
      2 19del WT 19del Erotinib+Chemotherapy WBRT
      3 L858R L858R L858R Gefitinib+Chemotherapy WBRT
      4 L858R WT WT Gefitinib+Chemotherapy WBRT
      5 19del WT WT Gefitinib+Chemotherapy WBRT
      6 L858R WT L858R/T790M Erotinib+Chemotherapy WBRT
      7 L858R WT WT Gefitinib WBRT
      8 19del 19Del 19Del/T790M Gefitinib WBRT
      9 L858R WT WT Erotinib+Chemotherapy NONE
      10 19del WT WT Erotinib+Chemotherapy WBRT
      11 19del WT WT Icotinib+Chemotherapy WBRT
      12 L858R WT L858R/T790M Chemotherapy WBRT
      13 L858R L858R WT Icotinib WBRT
      14 19del WT WT Gefitinib+Chemotherapy WBRT


      Conclusion:
      It was feasible to test EGFR mutation in CSF. CSF may serve as liquid biopsy of advanced ADC with BM by enabling measurement of cfDNA within CSF to characterize EGFR mutations.

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    P3.02c - Poster Session with Presenters Present (ID 472)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      P3.02c-020 - More Than 3 Years Long-Term Maintenance Treatment of Bevacizumab for Advanced-Stage NSCLC: A Report of Three Cases (Now Available) (ID 4743)

      W. Wu

      • Abstract
      • Slides

      Background:
      Bevacizumab has proven efficacy in extending OS and PFS as first-line treatment for advanced nonsquamous NSCLC.

      Methods:
      There were three advanced NSCLC patients received maintenance with bevacizumab for more than 3 years in our hospital, and here we share the data of these patients.

      Results:
      All three patients with advanced-stage lung adenocarcinoma received bevacizumab (15mg/kg) plus paclitaxel and carboplatin for 6 cycles as first-line treatment and bevacizumab maintenance. In the maintenance, proteinuria occurred in all three patients after 6 months of treatment or longer and caused cessation of bevacizumab in two patients. It’s noteworthy that two patients presented spleen changes after long-term maintenance. In patient 01, proteinuria occurred after 8 cycles of bevacizumab, caused cessation of 7 doses, and lasted till one year after discontinuation of bevacizumab. In patient 02, splenomegaly was found after 44 cycles of bevacizumab, caused treatment discontinuation, and reversed after 6 months of discontinuation. In patient 03, proteinuria occurred after 29 cycles of bevacizumab and caused cessation of 5 doses of bevacizumab. Besides, increased serum creatinine and blood urea nitrogen were found after 18 months of protienuria, and CT scan indicated wedge-shaped defects in spleen after 55 cycles. After disease progression or discontinuation of bevacizumab, two patients were confirmed harboring EGFR mutations and received EGFR TKI treatment. The other patient, EGFR mutation and ALK-arrangement negative, .received chemotherapy after disease progression. Figure 1



      Conclusion:
      These patients received bevacizumab maintenance for more than 3 years were all enrolled in clinical trials, and the long-term maintenance brought them adverse effects as well as clinical benefit. In the real world,the cycles of maintenance and the best total dosage of bevacizumab for NSCLC remain uncertain. Is it true that the longer the treatment lasts, the more benefit the patients get with the maintenance treatment of bevacizumab ?

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