Virtual Library

Start Your Search

D.S. Tan

Moderator of

  • +

    Management of NSCLC with resistance to first line targeted therapy (ID 21)

    • Event: ELCC 2017
    • Type: Educational session
    • Track:
    • Presentations: 4
    • +

      Management of drug resistance in ALK positive NSCLC (ID 86)

      09:00 - 10:30  |  Author(s): D.S. Tan

      • Abstract
      • Slides

      Abstract not provided

      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.

    • +

      Management of resistance in other targets beyond ALK and EGFR (ID 87)

      09:00 - 10:30  |  Author(s): L. Friboulet

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only 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, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      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.

    • +

      Management of T790M negative disease after EGFR TKI failure (ID 85)

      09:00 - 10:30  |  Author(s): M. Krebs

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only 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, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      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.

    • +

      Management of T790M positive disease after EGFR TKI failure (ID 84)

      09:00 - 10:30  |  Author(s): L. Horn

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only 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, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      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.



Author of

  • +

    Management of NSCLC with resistance to first line targeted therapy (ID 21)

    • Event: ELCC 2017
    • Type: Educational session
    • Track:
    • Presentations: 1
    • +

      Management of drug resistance in ALK positive NSCLC (ID 86)

      09:00 - 10:30  |  Author(s): D.S. Tan

      • Abstract
      • Slides

      Abstract not provided

      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.

  • +

    Poster Display Session (ID 63)

    • Event: ELCC 2017
    • Type: Poster Display Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
    • +

      131P - T790M co-exists with other secondary resistance mechanisms in EGFR mutation positive NSCLC and are associated with inferior outcomes (ID 159)

      12:30 - 13:00  |  Author(s): D.S. Tan

      • Abstract

      Background:
      Compared to conventional chemotherapy, NSCLC adenocarcinoma patients with EGFR-activating mutations (M+) have superior response to EGFR TKIs. However, all patients develop acquired resistance (AR) to TKIs, most commonly through T790M mutation. Due to intratumour heterogeneity, additional non-T790M mechanisms of AR could coexist with the T790M mutation. Little is known about the prevalence and clinical outcomes of patients with co-existing mechanisms of AR.

      Methods:
      145 patients with EGFR M+ NSCLC underwent a repeat biopsy after developing AR to TKI therapy. All specimens underwent histological review, while 116 (80%) underwent molecular profiling with multiple parallel high-sensitivity assays (including a 29-gene NGS panel) to detect genetic aberrations linked to TKI resistance. Kaplan Meier survival curves were plotted and compared with the log-rank test.

      Results:
      53.4% TKI-resistant patients (n = 57/106) were T790M-positive, while 61% patients had a non-T790M mechanism of AR including CMET polysomy or amplification, PTEN Loss, PIK3CA substitution and small cell change. 10 patients had lost their original EGFR-activating mutation. Up to 42% (n = 34/80) had a mutation in an NSCLC driver gene (including BRAF, DDR2, NRAS) detected by a 29-gene panel. 51% patients treated with 1[st]-generation gefitinib or erlotinib (n = 101) were T790M-positive, compared to only 20% of patients treated with 2[nd]-generation afatinib (n = 15). There was also a difference (p = 0.071) in T790M prevalence between patients treated with TKI post-progression (37/67, 55%) and those treated with chemotherapy (15/41, 36.5%). Notably, almost half the T790M-positive subjects harboured co-existing non-T790M mechanisms of AR (28/57, 49.1%). These patients had inferior OS of 42 months (95% CI 36.9-47.1) compared to patients with solely T790M (58 months, 95% CI 36.5-132.8).

      Conclusions:
      While T790M is widely-accepted as the predominant mechanism of AR, the spectrum of mutations can vary greatly depending on the type of prior therapy. Moreover, other mechanisms of AR could coexist with T790M and portend inferior clinical outcomes, suggesting that targeting other mechanisms of AR beyond T790M may be clinically-relevant.

      Clinical trial identification:


      Legal entity responsible for the study:
      Ministry of Health Singapore

      Funding:
      National Cancer Centre Singapore

      Disclosure:
      All authors have declared no conflicts of interest.