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H. Kimura



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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-010 - Analytical Performance of the cobas EGFR Mutation Assay for Japanese Non-Small Cell Lung Cancer (ID 1101)

      09:30 - 09:30  |  Author(s): H. Kimura

      • Abstract

      Background
      Patients’ EGFR mutation status prior to treatment impacts outcomes and, EGFR testing has been developed as a companion diagnostic; this relationship between therapeutic and diagnostic agents is known as personalized healthcare. Recently, it was reported that about half of patients may acquire resistance to EGFR-TKIs following therapy, mainly by appearance of EGFR mutations, such as T790M. Thus, it is important to assess EGFR mutation status before and during treatment to determine the most appropriate treatment regimens for patients. A number of PCR-based techniques are used in the assessment of EGFR mutations. In Japan, the “Scorpion-ARMS” therascreen® EGFR Rotor-Gene Q PCR Kitis (therascreen EGFR assay) the only available in vitro diagnostic (IVD) test. The cobas® EGFR Mutation Test (cobas EGFR assay) is the only FDA-approved kit for IVD testing in the US.In this study, we compared the performance of the cobas EGFR assay and the therascreen® EGFR assay using FFPE tissue specimens from NSCLC patients.

      Methods
      We extracted DNA from 149 FFPE tissues of NSCLC, according to the manufacturer’s instructions and performed a comparative study of cobas EGFR and therascreen EGFR methods.

      Results
      EGFR mutations were identified in 63 NSCLC specimens (42.3%) using the cobas EGFR assay and 61 samples (41.2%) using the therascreen EGFR assay. The concordance rate between the cobas EGFR assay and therascreen EGFR assays was 145/149 (97.3%). Only three discordants between these EGFR assays were observed. One T790M mutation in combination with an L858R mutation was identified by the cobas EGFR assay. No invalid assay results occurred with the cobas EGFR assay.

      Conclusion
      The cobas EGFR assay has two advantages. One is that the process is easily performed by stable methods. It takes only 8 hours, from tumor specimen to results generated using the semi-automated system. Thus, patients assessed using the cobas EGFR assay can begin the most appropriate treatment quickly. The other advantage is that only a very small amount of DNA (150 ng) is required to detect mutation status using the cobas EGFR assay. Our results show a high concordance rate (97.3%) of cobas EGFR with an existing IVD product, the therascreen EGFR assay. In this study, one double mutant, T790M in combination with L858R, was only identified by the cobas EGFR assay. The cobas EGFR assay appears to give the most accurate and appropriate results for NSCLC patients.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-045 - EGFR-TKI after disease progression with central nervous system metastasis in advanced non-small cell lung cancer with EGFR mutations (ID 3044)

      09:30 - 09:30  |  Author(s): H. Kimura

      • Abstract

      Background
      Several retrospective studies have reported that continued treatment with EGFR-TKI after developing progressive disease (PD) by RECIST improved survival compared to TKI-free treatment in NSCLC patients with EGFR mutations. However, it is unclear which patients would benefit from EGFR-TKI after PD. We hypothesized that patients with CNS progression only, without systemic deterioration, would show a good prognosis with EGFR-TKI after PD.Several retrospective studies have reported that continued treatment with EGFR-TKI after developing progressive disease (PD) by RECIST improved survival compared to TKI-free treatment in NSCLC patients with EGFR mutations. However, it is unclear which patients would benefit from EGFR-TKI after PD. We hypothesized that patients with CNS progression only, without systemic deterioration, would show a good prognosis with EGFR-TKI after PD.

      Methods
      In order to clarify the survival benefits in patients treated by EGFR-TKI after developing PD, particularly patients with CNS metastasis alone, NSCLC patients with EGFR mutations who were treated with EGFR-TKI and showed progression were analyzed retrospectively. The patients were categorized into two groups: patients continuing with EGFR-TKI treatment after progression (continuation group) and patients switched to chemotherapy or BSC (discontinuation group). Patients were also classified into two groups by site of progression: patients who showed deterioration involving only CNS metastasis (CNS progression group) and patients who showed progression of the primary lesion, lymph nodes, bone, liver, adrenal glands, CNS, or other sites (systemic progression group). Differences in post-EGFR-TKI progression survival (PPS) and overall survival were compared between the groups.

      Results
      A total of 160 patients, including 107 women, 116 light or never smokers, 156 patients with adenocarcinomas, and 130 patients with good performance status, were analyzed. There were 78 patients with deletions in exon 19, 69 patients with L858R, and 13 with minor mutations. At the time of the analysis, 111 patients showed disease progression by RECIST. No significant difference in the PPS was observed between the CNS progression group (n=29) and systemic progression group (n=82) (10.6 m vs. 11.2 m, p=0.90). Although it was not significant, the continuation group (n=43) showed longer PPS than the discontinuation group (n=68) (13.0 m vs. 9.7 m, p=0.06). The analysis of Cox hazards model including five variables (sex, smoking status, PS, continuation of EGFR-TKI, CNS progression or systemic progression) showed that the continuation of EGFR TKI beyond PD was the factor associated with longer PPS (HR=0.55, 0.31-0.92).

      Conclusion
      In this retrospective analysis, continued treatment with EGFR-TKI after PD resulted in longer PPS. A prospective study of continuation EGFR-TKI beyond REIST PD is needed.