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    P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P1.04-005 - Concurrent EGFR and ALK Mutations in KRAS-Mutant Lung Adenocarcinomas and Their Clinical Behavior (ID 1493)

      09:30 - 17:00  |  Author(s): B. Won

      • Abstract
      • Slides

      Background:
      KRAS represents the most commonly mutated oncogene in non-small cell lung cancer (20-30%). Multiple studies have suggested mutations of KRAS, epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) to be mutually exclusive[i], though there are few case studies showing coexisting EGFR and KRAS mutations[ii].

      Methods:
      We reviewed clinical genotyping data from 118 patients with stage I – IV KRAS mutated NSCLC. We investigated prevalence of concomitant EGFR and ALK mutations and evaluated clinical behavior in regards to overall survival (OS) and response to tyrosine kinase inhibitor therapy.

      Results:
      Among these 118 samples with KRAS alterations (codon 12 =98, 13 = 8, 61 = 3, 146 = 2, 189 =1, amplification = 6), median OS was 61.97 months (Graph 1). Concomitant EGFR mutations were noted in 6 subjects (5.0%) and ALK mutations were noted in 2 subjects (1.7%). One patient was found to have mutations of KRAS, EGFR, and ALK. These patients’ stage at diagnosis, response to TKI therapy (if utilized), and OS is documented in Table 1. Figure 1 Figure 2





      Conclusion:
      This analysis demonstrates it is possible for KRAS mutations to occur concurrently with EGFR and ALK missense mutations (not translocation) and emphasizes that a complete molecular analysis should be performed on all NSCLC patients. Further data is needed to more firmly elucidate how these concurrent mutations affect clinical behavior. Citations [I] Gainor JF, Varghese AM, Ou SH, et al. ALK rearrangements are mutually exclusive with mutations in EGFR and KRAS in non-small cell lung cancer. Clin Cancer Res. 2013 Aug 1; 19(15): 4273-81. [II] Zhu CQ, Sants GC, Ding K, et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group study BR.21. Journal of Clinical Oncology. 2008 Sep 10; 26(26): 4268-4275.

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