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K. Nishio



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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): K. Nishio

      • 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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    P3.09 - Poster Session 3 - Combined Modality (ID 214)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P3.09-007 - Update data of biomarker analysis of WJOG4107 (A randomized phase II trial of adjuvant chemotherapy with S-1 versus CDDP+S-1 for resected stage II-IIIA non-small cell lung cancer (NSCLC)) (ID 1504)

      09:30 - 09:30  |  Author(s): K. Nishio

      • Abstract

      Background
      We conducted a randomized phase II trial for patients with resected stage II-IIIA NSCLC comparing postoperative oral S-1 (80 mg/m2/day for consecutive 2 weeks q3w for 1 year) (S) (N=100) or cisplatin (CDDP) (60 mg/m2 day1) plus oral S-1, (80 mg/m2/day for 2 weeks) q3w for 4 cycles (PS)(N=100). We reported that disease free survival rate at 2 years (DFS@2) (95% confidence interval: CI), a primary endpoint, was 66 (55-74) % for S and 58 (48-67)% for PS. Here, we report the preliminary results of preplanned biomarker analysis, a co-primary endpoint, to identify molecules whose expression is significantly associated with patient outcome.

      Methods
      　cDNA extracted from macro-dissected formalin-fixed paraffin-embedded specimens were available for 197/200 patients. Thirty-one genes including those whose expressions have been potentially associated with　CDDP (e.g. ERCC1, XRCC1, BRCA1, GSTpi, HMG1, TBP) or fluorouracil (FU) sensitivity (TS, DHFR, DPD, UMPS, UPP1) were measured by QGE analysis (MassArray, Sequenom, CA). Additional analysis are being performed to assess ERCC1 isoform expression with an isoform-specific TaqMan probe (Applied Biosystems, CA). The expression of each gene was dichotomized according to its median value.

      Results
      Molecules such as ERCC1 and GSTpi whose expression have been previously associated with CDDP sensitivity did not emerge as predictive markers (P=0.7908, 0.6406, respectively). We quantitated ERCC1 by isotype (202 and 204 cannot be distinguished). There was a trend in patients with high 201 or 202/204, CDDP/S-1 was worse than S-1.

      Conclusion
      Quantitation of ERCC1 by isotype may define a patient subset that would benefit from postoperative platinum therapy.