Author of

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  P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall

  • 26258

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    P1.01-27 - Influence of EGFR-TKIs Treatment Lines and PFS on the Emergence of T790M Mutation (ID 13584)

    16:45 - 18:00  |  Author(s): Wanqiu Jia
    • Abstract
    • Slides

    Background
    

    For sensitizing EGFR mutation positive lung cancer patients, EGFR-TKIs can be used as the first-line or second-line (after chemotherapy) therapy according to NCCN guideline. However, whether different lines of EGFR-TKIs therapy or different PFS would affect the emergence of T790M, the leading cause of resistance to first and second generation of EGFR-TKIs was unknown.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We retrospectively analyzed 142 advance NSCLC patients with 93 patients received 1^st-line EGFR-TKIs, and 49 patients received 2^nd-line EGFR-TKIs after chemotherapy. EGFR sensitizing mutation and T790M mutation was detected simultaneously by hybridization capture-based NGS panel sequencing with tumor biopsy , ctDNA or pleural effusion samples.

    4c3880bb027f159e801041b1021e88e8 Result
    

    For the patients received 1^st-line EGFR-TKIs, 47 carried L858R mutation and 46 carried EX19del mutation; while patients received 2^nd-line EGFR-TKIs, 24 carried L858R mutation and 25 carried EX19del mutation. When those patients progressed on TKIs, T790M emerged in 25 of the 47 (53.19%) L858R carriers, and 23 of the 46 (50.00%) EX19del carriers with 1^st-line EGFR-TKIs (p=0.76). However, only 6 of the 24 (25.00%) L858R carriers yet 16 of the 25 (64.00%) EX19del carriers with 2^nd-line EGFR-TKIs had T790M detected (p=0.006). The incidence of T790M was significant lower in L858R carrier treated with 2^nd-line compared with 1^st-line EGFR-TKIs (25.00% vs 53.19%, p=0.023), however, there was no difference for EX19del carrier (50.00% vs 64.00%, p=0.26). To further analyzed whether different PFS affected the appearance of T790M, we divided patients into 3 groups as PFS≥13 months (n=48), PFS≤8 months (n=60) and the between (n=34). The incidence of T790M was significantly lower in the PFS≤8 months group compared with the PFS≥13 months (31.67% vs 62.5%, p=0.001). The difference was also significant if only counting the L858R carriers (18.52% vs 59.26%, p=0.002), but not significant in the EX19del carriers (42.42% vs 66.67%, p=0.082).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    1^st-line or 2^nd-line EGFR-TKIs generally did not significantly alter the emergence of T790M. But for the L858R mutation carriers, the incidence of T790M is significantly decreased if treated as a 2^nd-line EGFR-TKIs therapy. In addition, patients with longer PFS were associated with higher incidence of T790M mutation.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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