Author of

• 30601

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  P2.01 - Advanced NSCLC (ID 159)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30640

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    P2.01-39 - Serial Plasma ctDNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in T790M+ NSCLC (ID 2396)

    10:15 - 18:15  |  Author(s): Wei-Yu Liao
    • Abstract
    • Slides

    Background
    

    Recent advances in detection of genomic DNA from plasma samples allow us to follow the alteration of shedding tumor DNA in plasma before and after systemic treatment with multiple biopsies. Osimertinib is the standard of care for NSCLC patients with T790M mutations. We plan to use serial plasma cfDNA genomic alteration to predict osimertinib efficacy and search for possible resistance mechanisms.

    Method
    

    We prospectively collected plasma from patients of EGFR mutation-positive NSCLC who harbored acquired EGFR T790M mutation following prior EGFR-TKI therapy. Plasma samples were collected before starting osimertinib treatment, 4 weeks following osimertinib treatment and upon disease progression. ctDNA were detected by Guardant360 gene panel test.

    Result
    

    Fifteen patients (median age 62 [range 48-77], 53% men, 53% exon 19 deletion and 47% exon 21 L858R mutation) received osimertinib treatment. Acquired T790M mutation was diagnosed by using plasma sample only (Cobas® or digital PCR) (n = 11), tissue or pleural effusion only (n = 2), and both tissue and plasma samples (n = 2). Before starting osimertinib treatment, activating mutations were detected in plasma in all patients, T790M was detected in 93% (n = 14) and TP53 mutation was detected in 47% (n = 7) of the patients by using Guardant360. After osimertinib treatment, 11 out of the 14 patients had non-detectable plasma T790M at the 4^th week. Follow-up CT at least 8 weeks following osimertinib treatment of the 11 patients disclosed decreased tumor size (6 confirmed PR, 1 unconfirmed PR and 5 SD by RECIST criteria). The remaining 3 patients who had detectable plasma T790M (n = 2) or increased activating mutation allele frequency (n = 1) at the 4^th week had progressive disease within 16 weeks. The first patient had initial PR but later developed C797S on progression. The second patient developed new liver tumor following prior stable disease. This patient had baseline TP53 and CDKN2A mutations detected in the plasma, and allele frequencies decreased at the 4^th week and increased on progression. The last patient had rapid progression on osimertinib treatment, and alterations in PTEN and TP53 were detected on baseline and increased at the 4^th week and on progression. In that patient, T790M mutation was not detectable at the 4^th week but activating mutation increased in allele frequency at the 4^th week and on progression. Regarding patients with baseline TP53 mutation, 4 (57%) patients who had non-detectable plasma TP53 mutation at the 4^th week achieved disease control, and 2 (29%) patients had detectable or increased TP53 mutation allele frequency had PD within 16 weeks.

    Conclusion
    

    4 week plasma ctDNA following osimertinib treatment may predict early progression within 16 weeks.

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