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Junying Xu



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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.98 - NSCLC Patients With Rare EGFR Mutations in Exons 18 and 19 Benefits From Treatment With EGFR Tyrosine Kinase Inhibitors (ID 1057)

      00:00 - 00:00  |  Presenting Author(s): Junying Xu

      • Abstract
      • Slides

      Introduction

      EGFR tyrosine kinase inhibitors (TKI) were approved for NSCLC patients harboring either of the two classic EGFR mutations, L858R and exon 19 deletion. The sensitivity profile of mutations other than these two classic EGFR mutations in response to different generations of EGFR-TKI has been reported. However, treatment response and survival outcomes of patients with some rare mutations are poorly understood. In our study, we aimed to investigate the survival outcome of NSCLC patients with rare EGFR mutations.

      Methods

      We retrospectively screened the genomic data of 1,225 patients diagnosed with EGFR-mutant advanced NSCLC between September 2017 to November 2018 from 4 participating hospitals who submitted samples for next-generation sequencing at Burning Rock Biotech. Rare EGFR mutations were defined as mutations located on the tyrosine kinase domain with the exception of mutations with established therapeutic response profiles including exon 19 deletions, L858R, exon 20 insertions, G719X, T790M, L861Q, and S768I. We further analyzed the progression-free and overall survival outcomes for patients identified with rare EGFR mutations who had available survival data.

      Results

      Of the 1,225 EGFR-mutant, EGFR-TKI naïve advanced NSCLC patients screened, a total of 28 patients with rare EGFR mutations were identified. A majority of them (82.1%, 23/28) harbored single mutations, while the remaining 5 patients harbored compound EGFR mutations. EGFR L747X (n=5), E709_T710delinsD (n=3), G799F (n=2), K745_E746insIPVAIK (n=2), and compound in cis mutations L833V and H835L (n=2) were detected from more than 1 patient. Among the 33 rare EGFR mutations identified from our cohort, 4 mutations were novel and are not listed in the archives of the Catalogue of Somatic Mutations in Cancer (COSMIC), including G735C, M825L, A864P and S924C. Treatment response and survival outcomes were evaluated for 6 patients who received various generations of EGFR-TKI in the first-line setting. Patients with rare EGFR mutations in exon 18 including E709_T710delinsD, and compound EGFR S720F/L861R benefits from first- or second-generation EGFR-TKI therapy. Meanwhile, patients with rare EGFR mutations in exon 19 including G735C, K745_E746insIPVAIK, and L747P benefits from second- or third-generation EGFR-TKI therapy.

      Conclusion

      Patients with different EGFR mutations have distinct responses and outcomes to different generations of EGFR-TKI. Our study contributes an incremental step in understanding the clinical responses of patients with rare EGFR mutations located in exon 18 and 19. Understanding the treatment responses and survival outcomes are critical in the optimal treatment management and improving the survival outcomes of patients with rare EGFR mutations.

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