Author of

• 36336

  +

  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

  • 36409

    +

    P76.57 - Resistance Mechanisms to Osimertinib Upon it’s Line of Therapy in Patients with EGFR+ NSCLC and Beyond (ID 3183)

    00:00 - 00:00  |  Presenting Author(s): Vered Fuchs
    • Abstract
    • Slides

    Introduction
    

    : Osimertinib is a third-generation, CNS active TKI used to treat patients with non-small cell lung cancer and a mutation in the EGFR gene who progressed upon treatment with early generation TKIs and developed the T790M mutation, or according to current guidelines, as front-line treatment. To date, resistance mechanisms to osimertinib as second- or third-line treatment include EGFR related mutations such as C797S, amplification of MET, HER2, KRAS and PIK3CA. However, resistance mechanisms following first line therapy with osimertinib are currently a closed book. The FLAURA(1) trial was the first study to pave the way for this issue. This study aims to deepen the understanding and clarify possible mechanisms of osimertinib 1^st line resistance in comparison to the 2^nd line by examining cfDNA results of 30 patients who developed resistance to osimertinib. Furthermore, we followed clinical outcomes of chosen patients who received combined therapy following EGFR resistance, a novel strategy not yet widely tested.

    Methods
    

    Liquid biopsy technique (Guardant360) was used to monitor tumor dynamics in patients who were treated by osimertinib as for 1^st line therapy (Group A, N=15). We compared the findings with a group of patients who received osimertinib as second -line therapy (Group B, N=15).

    Results
    

    All but one patient presented existence of the primary EGFR mutation. While the C797S mutation was relatively common in the 2^nd line osimertinib setting (5/15), it did not develop in group A patients.TP53 was the most common detected mutation among all patients accounting for 11/15 group ANSG panels (73.33%) and 10/15 group B NSGpanels (66.67%). In group A MET amplification was found in 3/15 patients (20%). However, MET mutation appeared in only one patient from group B. Frequent mutations shared by both groups comprise MET, KRAS, MYC, ARID1A.

    Conclusion
    

    Resistance mechanisms to osimertinib as first line therapy differ from those which develop in a second line setting. TP53 may have clinical relevance in progression of the disease. MET amplification was found in a substantial percentage of group A patients raising the possibility of it being a probable resistance mechanism.Compared to patients receiving osimertinib as second line treatment, in treatment naïve patients the C797S is not necessarily a leading resistance mechanism. Combined therapy was effective and well tolerated, making it a decent choice in patients for whom there is a reasonable rationale for such treatment.

    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.