Author of

• 36336

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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

  • 36381

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    P76.39 - Acquired Resistance Mechanisms in T790M-Positive Advanced NSCLC Tested by Non-Invasive Molecular Testing (NIMT) and Their Clinical Relevance (ID 1803)

    00:00 - 00:00  |  Presenting Author(s): Piyakarn Watcharenwong
    • Abstract
    • Slides

    Introduction
    

    There is currently limited knowledge of resistant mechanisms after failure of Osimertinib treatment in T790M-positive NSCLC in Asia. We used Non-Invasive Molecular Testing (NIMT) to explore the acquired resistant mechanisms to Osimertinib and their clinical relevancies.

    Methods
    

    This study was performed from January 2016 to December 2019 in T790M-positive NSCLC patients who received Osimertinib after failure of 1^st/2^nd generation EGFR-TKI treatment in Ramathibodi Hospital lung cancer database. We included patients who had plasma samples before treatment and at disease progression. The paired plasma samples were analyzed for resistant mechanisms by NGS (Thermofisher Pancancer 52 genes) then correlated with clinical outcomes.

    Results
    

    The 100 plasma samples from 50 patients were included (17 Males; 33 Females). The median age was 63.5 year-old. The majority of patients were non-smoker (82%) and adenocarcinoma (98%). Types of preexisting mutations were exon 19 deletion (60%), and exon 21 L858R (32%). Most of the patients used Osimertinib as 2^nd-line treatment (68%). The response rates were 52% PR, 34% SD, and 14% PD. Nineteen patients (38%) developed more than one resistant alteration. The T790M-loss was most commonly found (50%), followed by PIK3CA (14%), EGFR C797S / HER2 / FGFR2 mutation (10% of each mutation) and EGFR (L792F, P848L/Q)/ BRAF/ RET/ KIT mutation (8% of each mutation), MET mutation (6%), MET exon 14 skipping (4%), MET amplification (2%) and small cell transformation (2%), and so on. EGFR C797S was found only in T790M-maintained patients. The median time to treatment failure (TTF) for taking Osimertinib in all patients was 9.3 mo. The patients with T790M-loss tended to have shorter TTF than the patients with T790M-maintained [median TTF 6.0 vs 10.1 months (mo), P=0.21]. Patients who developed T790M-maintained with C797S had tended of shorter OS compared to T790M-maintained without C797S (11.0 vs 15.2 mo). Furthermore, patients with T790M-loss together with other co-mutations had shorter TTF compared to patients with T790M-loss without other co-mutations (4.1 vs. 10.6 mo, adjusted HR 5.38, P=0.07) (Figure1). The patient who had brain metastasis before using Osimertinib significantly related to T790M-loss and patient who developed brain progression was related to BRAF mutation.

    Conclusion
    

    There were heterogeneous mechanisms of acquired resistance to Osimertinib in T790M-positive NSCLC. The patient with T790M-loss tended to have poorer survival compared to T790M-maintained patients. C797S and T790M loss with other co-mutation are the important factors affected the survival outcomes in this group of patients.

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