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Nuria Mancheno



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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      29P - Pretreatment T790M mutation detection by ultrasensitive PCR assay as predictor of efficacy in non-small lung cancer (NSCLC) patients treated with 1<sup>st</sup> or 2<sup>nd</sup> generation EGFR tyrosine kinase inhibitors (TKIs) (ID 477)

      12:30 - 13:00  |  Author(s): Nuria Mancheno

      • Abstract
      • Slides

      Background

      T790M mutation detection previos to 1st/2nd generation EGFR TKIs treatmentis rare by conventional methods (1-8%), although PCR ultrasensitive methods increase their prevalence to 34-80%. The aim of the study is to evaluate the presence of T790M mutations by 2 different ultrasensitive assays and their impact efficacy.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      127 patients (pts) with NSCLC and EGFR mutations were analyzed. 73 of them had sufficient pretreatment tissue for T790M testing. The T790M mutation was screened by PNA Clamp TaqMan Assay (Applied Biosystems) and by ddPCR (BioRad).

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      The limit of detection (LOD) of variant allele frequency was 0.081% and 0.136% for PNA Clamp and ddPCR, respectively. Prevalence of T790M mutations pretreatment was 23% (17/73) and 32% (23/71), respectively. A total of 71 samples gave a certain result in both methodologies (71/73; 95.89%). Agreement between the results of both techniques was 91.55%. Finally, 31 pts who met the eligibility criteria: diagnoses of advanced NSCLC, treated with 1st/2on generation TKIs, have pre-treatment tissue for the analysis and the result of the T790M ultrasensitive analysis was conclusive; were selected to assess the relationship between the results of T790M determined by ultrasensitive methods and the prognosis. Nine (29%) of them had pretreatment T790M+ mutation by both ultrasensitive methods. Median PFS and OS were superior for patients with T790M detected by ultrasensitive PCR assay pre-treatment with TKIs: 24,9 vs. 19,6 m (p = 0.107) and 47,3 vs. 19,9 m (p = 0.76), respectively. To evaluate the association between T790M pretreatment and in the moment of progression we selected 16 pts with T790M mutation analyzed at progression (8 T790M+ and 8 T790M-). T790M at the time of progression was detected in 7 (63,6%) of 11 T790M- diagnosis patients, whilst only 1 (20%) of 5 T790M+ diagnosis patients were positive at the time of progression.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Both methods were highly effective for detection of EGFR T790M mutation. The detection of T790M mutation pretreatment of 1st/2ndgeneration EGFR TKIs by ultrasensitive PCR assay was associated with better PFS and OS.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      Precision Medicine and Biomarkers Unit. IISLAFE.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca.

      682889d0a1d3b50267a69346a750433d Disclosure

      O.J. Juan Vidal: Honoraria, advisory role: Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche/Genetech, AstraZeneca, Pfizer, Eli Lilly, AbbVie; Institutional research funding: Bristol-Myers Squibb, AstraZeneca. All other authors have declared no conflicts of interest.

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