Author of

• 11454

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  P2.01 - Poster Session 2 - Cancer Biology (ID 145)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11469

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    P2.01-015 - Gene expression of MAGE-A3 and PRAME tumor antigens and EGFR mutational status in lung adenocarcinoma in a German center (ID 2700)

    09:30 - 09:30  |  Author(s): A. De Creus
    • Abstract

    Background
    The MAGE-A3 and PRAME tumor antigens are potential targets for cancer immunotherapy. In patients with non-small cell lung cancer (NSCLC), specific mutations of the epidermal growth factor receptor (EGFR) gene are associated with improved therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs); mutations in the KRAS gene confer resistance to EGFR-TKIs. In NSCLC, EGFR and KRAS mutations are predominantly found in adenocarcinomas. The relationship between MAGE-A3 or PRAME expression and EGFR/KRAS mutational status is unknown. The presence of specific EGFR mutations determines the selection of patients for EGFR-TKIs therapy. With cancer immunotherapeutics and EGFR-TKIs potentially moving on to the same treatment stages, it is important to determine whether patients eligible for EGFR-TKI therapies might be also eligible for treatment with MAGE-A3 or PRAME cancer immunotherapeutics. We have previously reported that MAGE-A3 and PRAME were expressed in 36% and 66% of NSCLC tumor samples, and in 27% and 44% of adenocarcinoma samples, respectively (Linder et al. ASCO 2012). Here we report the MAGE-A3 and PRAME expression rates and mutational status of EGFR and KRAS in NSCLC adenocarcinoma.

    Methods
    This was a single-center, non-interventional, retrospective study conducted at the Lungenklinik Hemer (Germany). MAGE-A3 and PRAME mRNA expression patterns in patients with pathologically proven stage I, II or III NSCLC were determined by quantitative real-time PCR on formalin-fixed paraffin-embedded (FFPE) tumor samples. EGFR and KRAS mutational status was analyzed on DNA extracted from FFPE samples using laboratory-developed PCR-based assays. Samples from patients with adenocarcinoma i.e. adenocarcinoma, bronchoalveolar adenocarcinoma, adenosquamous carcinoma, for which MAGE-A3 and/or PRAME expression results were available were selected for this analysis.

    Results
    Out of 311 samples, 277 and 287 produced valid results for EGFR and KRAS mutational status, respectively. EGFR mutations were found in 10.1%, and KRAS mutations in 33.8% of samples. The association between MAGE-A3 or PRAME expression and EGFR mutational status is shown (table). Figure 1 EGFR mutational status was not associated with MAGE-A3 expression but was significantly associated with PRAME expression (table). There was no association between KRAS mutational status and MAGE-A3 (P=0.6109) or PRAME (P=0.8983) expression.

    Conclusion
    In this study, tumor samples expressing PRAME tended to be associated with wild-type EGFR status. Thus, among patients with PRAME-positive tumors, only very few would be eligible for EGFR-TKI therapy. This indicates a potentially straightforward treatment choice for patients and physicians, should EGFR-TKIs and PRAME cancer immunotherapeutics become available for similar indications. Funding: GlaxoSmithKline Biologicals SA.