Virtual Library

Start Your Search

Yael Fisher



Author of

  • +

    EP1.14 - Targeted Therapy (ID 204)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
    • +

      EP1.14-12 - KRAS Exon 2 Mutation - A Resistance Pathway to 1st and 2nd Generation EGFR TKIs (Now Available) (ID 1353)

      08:00 - 18:00  |  Author(s): Yael Fisher

      • Abstract
      • Slides

      Background

      The most common resistance pathway to first and second generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in advanced non-small cell lung cancer (aNSCLC) is acquired EGFR T790M mutation. Other resistance mechanisms composed of amplifications of MET, HER-2 and small cell transformation. Acquired KRAS mutation is known as resistance mechanism to 3rd generation EGFR TKIs, but not to 1st or 2nd generation.

      Method

      Patients with EGFR positive NSCLC had molecular profiling done upon resistance to 1st or 2nd generation EGFR TKIs, done by next generation sequencing on FFPE tissue or cfDNA from plasma including EGFR exons 19, 20, 21, KRAS exon 2 and BRAF exon 15. Treatment outcomes and prognosis data were taken from the medical records.

      Result

      Fifty-three EGFR positive NSCLC patients had molecular profiling done upon resistance to 1st or 2nd generation EGFR TKIs since August 2017, of them 48 had KRAS exon 2 mutation tested. Six (12.5%) patients had KRAS exon 2 mutation, found on plasma in 5 patients and in tissue in 1 patient. Of the 6 patients, the original EGFR mutation was found in 3 patients (50%), and 2 had concurrent EGFR T790M mutation. One patient had KRAS mutation on the initial EGFR testing, although had prolong response to EGFR TKIs.

      All patients responded to 1st line EGFR TKIs. Upon progression- the 3 patients tested positive for EGFR T790M mutation were treated with osimertinib, although only 1 patient with concurrent KRAS and EGFR T790M mutation responded, and 2 patients with no EGFR T790M mutation were treated with chemotherapy with progressive disease.

      Conclusion

      We found acquired KRAS mutation as resistance mechanism for EGFR TKIs in 12.5% of patients with EGFR positive NSCLC treated with 1st or 2nd generation EGFR TKIs.

      The patients with NSCLC tested positive for KRAS as resistance mechanism for EGFR TKIs were characterized by poor response to either TKIs or chemotherapy. Therefore, testing for KRAS exon 2 mutation is advised upon disease progression during EGFR TKI therapy.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.