Author of

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  MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Targeted Therapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 13:30 - 15:00, Room 107

  • 26034

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    MA15.05 - The Mutational Profiles of EGFR 19 Exon Deletion and 21 Exon L858R Mutation and Their Association with Primary Response to EGFR-TKIs (ID 12671)

    14:00 - 14:05  |  Author(s): Caichen Li
    • Abstract
    • Presentation
    • Slides

    Background
    

    In addition to the known resistant genetic alterations, such as de novo T790M and TP53 mutations, some recent studies suggested that other concomitant mutations might also compromise the efficacy of EGFR-TKIs. Meanwhile, it has been widely observed that EGFR 19 exon deletion (19del) was associated with better outcomes in treatments with EGFR-TKIs than L858R mutation (L858R). It is of interest to explore whether the respective mutational profiles of 19del and L858R may explain their different sensitivity to EGFR-TKIs.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We obtained individual patient data from 7 studies (including 1 from our center) using next generation sequencing to comprehensively determine the mutational profile of EGFR mutated patients. As different panels were used by different studies, we analyzed T790M, TP53 and the loci that were reported by at least 4 studies (half of the included ones).

    4c3880bb027f159e801041b1021e88e8 Result
    

    A total of 250 19del and 279 L858R patients were included. We found similar prevalence of all co-mutations (19del 65.2% vs. L858R 64.2%), TP53 (19del 36.8% vs. L858R 40.9%), APC, BRAF, PIK3CA, STK11, PDGFRA, PTEN, AKT1 and KIT between the two types, except for de novo T790M (19del 34.4% vs. L858R 50%, P=0.07), CDKN2A (19del 10.5% vs. L858R 3.4%, P=0.03) and KRAS (19del 0.5% vs. L858R 4.0%, P=0.01). In addition, the number of co-mutations was equivalent between the two types (19del 0.95±0.95 vs. L858R 0.93±0.90, P=1.00). Through multivariate logistic regression, we found that EGFR mutation type, de novo T790M, TP53 and other co-mutations, all had independent adverse effects on primary response rate. Consistently, we found that in those without co-mutations, 19del still showed better outcomes compared with L858R (pure EGFR mutations: 19del 88.0% vs. L858R 68.4%), and that the response rates in both mutation types decreased in the same extent when contaminated with other mutations (EGFR mutations with co-mutations: 19del 53.1% vs. L858R 30.0%).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Our study demonstrated that the presence of T790M, TP53 and other concomitant mutations indicated poor response to EGFR-TKIs, but most of them showed similar prevalence between 19del and L858R. Patients with L858R showed significantly less response than those with 19del regardless of the co-mutation status, indicating that some intrinsic factors and potentially de novo T790M, rather than other co-mutations, might underlie the different sensitivity of 19del and L858R to EGFR-TKIs.

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