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D. Chen



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    MA 12 - Circumventing EGFR Resistance (ID 665)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Advanced NSCLC
    • Presentations: 1
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      MA 12.11 - The Alteration of T790M Prevalence Between 19 Deletions and L858R in NSCLC After EGFR-TKIs Therapy, a Meta-Analysis (ID 10077)

      12:10 - 12:15  |  Author(s): D. Chen

      • Abstract
      • Presentation
      • Slides

      Background:
      Pre-treatment EGFR T790M mutation is more likely to coexist with L858R mutation than with exon 19 deletions (19del) in NSCLC. However, EGFR-TKIs might alter this status. We sought to compare the prevalence of T790M upon acquired resistance to EGFR-TKIs between 19del and L858R by assembling all existed data.

      Method:
      Electronic databases were comprehensively searched for eligible studies. The primary endpoint was the odds ratio (OR) of T790M mutation in NSCLC co-existing with L858R mutation and 19del upon resistance to first-generation EGFR-TKIs. A random effects model was used. Stratified analysis was performed based on study type (retrospective and prospective), race (Asians and Caucasians) and sample type (tissue and plasma).

      Result:
      A total of 25 studies involving 1,770 patients were included. The overall T790M existent rate was 45.25%. Post-resistance T790M was more frequent in 19del than in L858R mutated patients (53% vs. 36%; OR 1.87; p=0.00). All outcomes of subgroup and overall analyses were similar. In contrast, we re-analyzed the previous meta-analysis, finding that the pooled rate of pretreatment T790M was 14% and 22% in 19del and L858R respectively (OR 0.59; p<0.01). The increase of T790M rate was 2.79-fold in 19del and only 0.63-fold in L858R in the course of EGFR-TKIs therapy.

      Conclusion:
      Opposite to the situation of de novo T790M, it was observed that T790M was more frequent in exon 19del than in L858R among EGFR-TKI resistant acquired patients. The difference in T790M alteration between 19del and L858R encourages development of specific resistance mechanism detection or treatment strategies.

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