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C. Joelet

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    P3.02b - Poster Session with Presenters Present (ID 494)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02b-102 - Osimertinib Benefit in ctDNA T790M Positive, EGFR-Mutant NSCLC Patients (ID 5472)

      14:30 - 15:45  |  Author(s): C. Joelet

      • Abstract
      • Slides

      The third generation tyrosine kinase inhibitors (TKIs) osimertinib is approved for patients with acquired epidermal growth factor receptor (EGFR) T790M mutations in advanced non-small cell lung cancer (NSCLC) patients. New tissue biopsy to detect T790M cannot always be performed, due to the size or location of the lesions and risk of complications to the patient. As an alternative, liquid biopsies based on circulating cell-free tumor DNA (ctDNA) analysis have been described. We assess the efficacy of osimertinib in ctDNA T790M-positive, EGFR-mutant NSCLC patients with progression under first- or second-generation EGFR TKIs ineligible for tissue biopsy at progression; and the feasibility of identifying T790M mutations in ctDNA isolated from blood samples in this cohort of patients.

      ctDNA analysis using enhanced eTAm-Seq™ assay (Inivata), and enhanced version of the Tam-Seq ® assay was conducted in 48 eligible patients treated in a single center between April 2015 and April 2016. Patients determined to have T790M mutation were prescribed osimertinib (80mg daily). Objective response rate (ORR) by RECIST 1.1 criteria was centrally reviewed and correlated with (A) T790M allele fraction, (B) EGFR activating mutation allele fraction, and (C) T790M by EGFR activating mutation allele fraction ratio.

      T790M status in ctDNA was assessed in 48 EGFR-mutant NSCLC patients. Median age was 65 years (range 37-83); 36 (75%) patients were women and 58% were never-smoker. EGFR mutation status was Del19 in 33 (69%) and L858R in 15 (31%) NSCLC patients. The ctDNA T790M mutation was positive in 24 out of 48 (50%) patients, and 23 out of 24 T790M-positive samples maintained the original activating EGFR mutation in ctDNA analysis. Among evaluable patients (n=16), osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. Neither correlation between ctDNA T790M AF and RECIST radiological response was observed, nor with the other parameters evaluated. Of the seven cases with best response (decrease of 50% or more in size), 3 cases had T790M detected at <0.25%.

      Osimertinib efficacy in a real-world setting among T790M-positive tumours detected in ctDNA from liquid biopsy support the use of such liquid biopsies as a surrogate marker for T790M in tumour tissue, avoiding the need for invasive tumor biopsies for personalising treatment in lung cancer patients

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