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Xin Yu



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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
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      P76.45 - Evolution of Epidermal Growth Factor Receptor (EGFR) Gene Mutations in EGFR-TKIs Treated Chinese NSCLC (ID 2124)

      00:00 - 00:00  |  Presenting Author(s): Xin Yu

      • Abstract
      • Slides

      Introduction

      Mutations in epidermal growth factor receptor(EGFR) gene such as ex19del, L858R and T790M are leading oncogenic alternatives in NSCLC and more common in Chinese. Patients carried targeted EGFR mutations are routinely treated with EGFR-TKIs. How the EGFR driver mutations change after TKI treatment remains a controversial issue. In this real world study, we employed longitudinal analysis in a EGFR-TKI treated cohort and clarify the dynamic changes of EGFR alternatives.

      Methods

      483 NSCLCs were diagnosed between Jan 2017 and Dec 2019. The median follow-up time is 206 days. Each patient underwent EGFR-TKI treatment and accepted at least two follow-up molecular evaluations, via NGS and ddPCR methods applied on tumor samples including tissue, plasma DNA and pleural effusion.

      Results

      473 cases were EGFR-mut positive at the time of first detection. Ex19del (n=242) and L858R (n=215) were dominant and mutually exclusive in majority, with only 1 (0.21%) exception. T790M preferred to co-exist with ex19del than L858R (18.2% vs 10.7%). 182 cases kept harboring the same EGFR driver mutations with a median follow-up time of 97 days (28 cases with more than 1 year), 176 of which carried either ex19del or L858R exclusively and only 7 accompanied with T790M. In the other 288 cases we observed EGFR driver mutations changed. 28 cases become EGFR-naïve with a median time of 388 days, while 5 of them relapsed in following time. 260 cases kept EGFR-mut positive with EGFR evolutions and among them, disappearance of ex19del and L858R occurred in 4 cases and 8 cases, respectively. The newly emerged EGFR mutations, including T790M (n=3 for ex19del group, n=6 for L858R group), S229C (n=1 for ex19del group), E602K (n=1 for L858R group) and V60M (n=1 for L858R group) had no co-current mutation. Among 26 cases detected C797X, 18 cases were initially T790M-accompanied and emerged to carry C797X within a relatively short time (median 12 days), while 8 cases initially with single driver mutation (6 of ex19del, 2 of L858R) evolved to harbor C797X after relatively long treatment time (median 449 days). 10 cases were EGFR-naïve at the time of first detection yet turned to be positive with a median time of 203 days.

      figure1.evolution of egfr mutaions in patients.png

      Conclusion

      Ex19del and L858R are dominant oncogenic alternatives and tend to maintain in NSCLC even during TKI treatment. The probability of their disappearance is quite small, often happened after 1-year TKI treatment and mainly replaced by T790M. C797X only emerges in patients harboring T790M subsequently soon.

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