Virtual Library

Start Your Search

S. Negoro



Author of

  • +

    MO06 - NSCLC - Chemotherapy I (ID 108)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MO06.02 - Monitoring EGFR T790M with plasma DNA in lung cancer patients treated with EGFR tyrosine kinase inhibitor in prospective observational study (ID 1399)

      16:20 - 16:25  |  Author(s): S. Negoro

      • Abstract
      • Presentation
      • Slides

      Background
      Detection of mutations with plasma DNA isolated from peripheral blood is an alternative method of biopsy. The gatekeeper T790M mutation of EGFR has been observed in half of patients who acquired resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI). Considering that majority of lung cancer recurrence occurs as distant metastases, determination of T790M using a non-invasive mutation detection system with plasma DNA would be useful. We recently developed a novel non-invasive, fully-automated monitoring system, MBP-QP (mutation-biased PCR and quenching probe) method, to detect T790M using plasma DNA. The detection limit was two copies of control plasmid and 0.2 ng of genomic DNA, the T790M mutation was detected in plasma DNA from 53% of lung adenocarcinoma patients who acquired resistance in the previous retrospective study. Compared with the other methods such as PNA-LNA PCR clamp, the cycleave PCR technique, and digital PCR, the MBP-QP method is simple, sensitive, and reflective of clinical course. To determine the usefulness of the MBP-QP method for monitoring T790M during treatment of EGFR-TKI, a prospective clinical study has been performed.

      Methods
      This is a prospective, multicenter observational study involving lung adenocarcinoma patients carrying EGFR activating mutations such as L858R and exon 19 deletions treated with EGFR-TKI. Primary objective was to determine whether T790M was detected with plasma DNA at the time point of progressive disease (PD), and the secondary objective was correspondence of T790M with plasma and cancer specimens. The association between detection of T790M and effect of EGFR-TKI were also investigated as the exploratory objective. Plasma DNA was isolated from the patients before treatment of EGFR-TKI, every four months during treatment, at the time of occurrence of PD, and after two courses of post-chemotherapy.

      Results
      Ninety lung adenocarcinoma patients treated with EGFR-TKI were enrolled, in whom 51% of L858R and 49% of exon 19 deletions were determined in tumor specimens before treatment. Most of the patients, 92.1%, had adenocarcinoma. 62% (55/90) was stage IV, and 29% (26/90) had postoperative recurrent disease. 43% (38/90) of the patients were treated with EGFR-TKI as the first-line therapy, and the rest of them were previously treated including 17% of the patients experienced with EGFR-TKI. T790M was detected in 23% (21/90) among the entire patients. Forty patients showed PD two years after beginning of this trial, and T790M was detected in 13 patients among the patients who acquired resistance to EGFR-TKI; the frquency of T790M positive among the patients with PD was 32.5% (13/40). Although T790M was temporarily detected during treatment of EGFR-TKI in 8 patients who were still responded to EGFR-TKI, is disappeared after that.

      Conclusion
      T790M was detected in plasma DNA isolated from lung cancer patients whose diseases were progressed. Continuous detection of T790M in plasma DNA seemed to be related with occurrence of PD.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      P2.10-014 - A phase II study of bevacizumab in combination with carboplatin and paclitaxel in patients with non-squamous (Non-Sq) non-small-cell lung cancer (NSCLC) harboring Mutations of Epidermal Growth Factor Receptor (EGFR) gene after failing First-line EGFR-Tyrosine Kinase Inhibitors (TKIs) Hanshin Oncology Group 0109 (ID 1054)

      09:30 - 09:30  |  Author(s): S. Negoro

      • Abstract

      Background
      EGFR-TKIs’ mono-therapy is one of the standard 1[st] line therapy for NSCLC harboring EGFR gene mutations. Although platinum doublet ± bevacizumab recommended for 2nd line therapy after failing EGFR-TKIs in National Comprehensive Cancer Network guideline, there is little information of these setting. Therefore, we planned prospective phaseⅡ study to evaluate the efficacy and safety of bevacizumab in combination with carboplatin and paclitaxel(PCB) for EGFR-TKIs resistant Non-Sq NSCLC.

      Methods
      In multicenter phase II trial, we recruited non-squamous NSCLC harboring EGFR gene mutation after failing EGFR-TKIs. Key eligibility criteria were as follows: Non-Sq NSCLC with EGFR mutation, failure of 1[st] line EGFR-TKIs, stageIIIB or IV or recurrence after surgery, measurable lesion, age 20 or over, ECOG Performance status (PS) 0 or 1, adequate organ function. Clinically significant hemoptysis, symptomatic brain metastasis, uncontrollable hypertension, interstitial pneumonia were excluded. Patients received carboplatin (AUC=6/5), paclitaxel (200mg/m2), bevacizumab (15mg/kg) intravenously on day1 every 3 weeks for three to six cycles, and bevacizumab was administered every 3 weeks until disease progression or intolerable toxic effects. Primary endpoint was response rate (RR) and secondary endpoints were progression free survival (PFS), overall survival (OS), disease control rate (DCR) and safety.

      Results
      A total of 31 patients were assigned between March 2010 and February 2013. One patient was excluded because of unfitted eligibility criteria. Therefore, we analyzed thirty patients’ data. Median age was 60 years (45~74), male/female : 11/19, PS 0/1 : 9/21, non-smoker/smoker : 18/12, EGFR mutation status exon19 del/exon21 L858R : 20/11, 1[st] line EGFR-TKIs gefitinib/erlotinib/other : 22/7/1. RR : 40% (95%CI:22%-58%), DCR : 83% (95%CI:70%-97%), PFS : 6.0 month (95%CI:4.8-12.2). Major severe adverse event (Grade 3,4) were one patient with dyspnea (G4), 6 with fever neutropenia (G3) and 3 patients with hyper tension (G3). There was no grade 5 adverse event.

      Conclusion
      In patients with Non-Sq NSCLC harboring EGFR gene mutation failed 1[st] line EGFR-TKIs, RR of 2[nd] line PCB therapy was lower than it was in 1[st ]line phase II study of PCB in Japan, but same RR of E4599 study. Safety was similar to previous reports. We considered PCB therapy is one of the treatment option in 2[nd]-line for patient with EGFR-TKIs resistant Non-Sq NSCLC.