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J.E. Yi



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    MINI 13 - Genetic Alterations and Testing (ID 120)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI13.14 - S768I Mutation in the EGFR Gene in Patients with Lung Cancer (ID 325)

      12:00 - 12:05  |  Author(s): J.E. Yi

      • Abstract
      • Presentation
      • Slides

      Background:
      Epidermal growth factor receptor (EGFR) mutations are relatively common oncogenic drivers in non-small cell lung cancer (NSCLC). Interestingly a number of patients have more than one mutation in EGFR. In order to understand whether these patients respond to EGFR inhibition, we reviewed our experience treating these patients. Herein we describe the Mayo Clinic experience with the S768I mutation of exon 20 of the EGFR gene.

      Methods:
      Relevant clinical and laboratory data were abstracted for selected cases, including evaluation of response after treatment with TKIs using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Inclusion criteria were cases including EGFR S768I mutation performed at Mayo Clinic or elsewhere until December 2014. EGFR testing was performed following microscopic examination by a pathologist to identify and select areas of tumor for macrodissection and confirm sufficient tumor percent. The EGFR test is a PCR based assay employing allele specific amplification and is used to test for mutations within exons 18-21 of the EGFR gene, most recently using the FDA approved platform. When testing was performed elsewhere, bidirectional sequencing was used.

      Results:
      1,527 cases of NSCLC that underwent EGFR testing were reviewed and the S678I mutation was present in 9 patients (0.59%), 4 of which were female. Median age at diagnosis was 61 years (range 49-68 years), 5 patients were never smokers and no subjects were current smokers at the time of diagnosis. The stage at diagnosis was I in 2, III in 3 and IV in 4 patients, respectively. All specimens were adenocarcinomas with 5 of them being grade 3. Only 3 cases had an isolated S768I mutation, 4 cases had a concurrent G719S mutation and 2 cases had a concurrent L858R mutation. The tumor responses of patients with stage IV disease are shown in the table. One patient with a concurrent S768I and L858R mutation with stage IIIa disease received curative intent lobectomy after neoadjuvant treatment with erlotinib. Erlotinib was discontinued in one case due to fatigue. Table: Response of S768I mutations to erlotinib by RECIST 1.1

      Mutation(s) Best response on erlotinib PFS (months) Overall survival (months)
      S768I alone Progressive disease 3 5
      S768I + G719 Partial response 6 23
      S768I + G719S Stable disease 12 33
      S768I + L858R Stable disease 30 51+


      Conclusion:
      S768I mutations in exon 20 of the EGFR are rare and are commonly seen in conjunction with common EGFR mutations. Due to its rarity and the variability of responses of treated cases, its exact prognostic and predictive role is not fully understood. Better understanding of its function and sensitivity to newer TKIs will allow for better management of patients with this mutation.

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    ORAL 23 - Prevention and Cancer Risk (ID 121)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Prevention and Tobacco Control
    • Presentations: 1
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      ORAL23.01 - A Randomized Phase IIb Trial of Myo-Inositol in Smokers with Bronchial Dysplasia (ID 856)

      10:45 - 10:56  |  Author(s): J.E. Yi

      • Abstract
      • Presentation
      • Slides

      Background:
      Previous preclinical studies and a phase I clinical trial suggested myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled, phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia.

      Methods:
      Smokers with ≥1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once/day for two weeks, and then twice/day for 6 months. The primary endpoint was change in dysplasia rate after six months of intervention on a per participant basis. Other trial endpoints reported herein include Ki-67 labeling index and pro-inflammatory, oxidant/anti-oxidant biomarker levels in blood and bronchoalveolar lavage fluid (BAL).

      Results:
      Seventy four (n=38 myo-inositol, n=36 placebo) participants with a baseline and 6-month bronchoscopy were included in all efficacy analyses. The complete response and the progressive disease rates were 26.3% versus 13.9% and 47.4% versus 33.3%, respectively, in the myo-inositol and placebo arms (p=0.76). The mean percent change in Ki67 labeling index in bronchial biopsies with dysplasia was -22.8% and -6.2%, respectively, in the myo-inositol and placebo arms (p=0.34). Compared with placebo, myo-inositol intervention significantly reduced IL-6 levels in BAL over 6 months (p=0.03) and had borderline significant effects on BAL myeloperoxidase (p= 0.06) level.

      Conclusion:
      The heterogeneous response to myo-inositol suggests a targeted therapy approach based on molecular alterations is needed in future clinical trials to determine the efficacy of myo-inositol as a chemopreventive agent.

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