Author of

• 18374

  +

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

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18405

    +

    P3.02b-031 - T790M: A Favorable Mutation? (ID 5681)

    14:30 - 14:30  |  Author(s): Y. Yu
    • Abstract

    Background:
    Patients with lung adenocarcinoma harboring somatic activating mutations in the epidermal growth factor receptor (EGFR) gene have benefited significantly from EGFR tyrosine kinase inhibitors (TKIs). However, a vast majority would eventually develop resistance to such TKIs, resulting in disease progression. T790M, a secondary mutation in exon 20 of the EGFR gene, has been identified as the major mechanism responsible for acquired EGFR-TKI resistance, accounting for roughly 50% of resistance. However, the association of T790M status and clinical outcome remains elusive. Here, we conducted a retrospective study examining the association between T790M status and prognosis on clinical samples obtained from 43patietns with EGFR-mutant lung adenocarcinoma and later acquired resistance to EGFR-TKIs.
    
    Methods:
    We performed capture-based targeted ultra-deep sequencing on either tumor biopsies or blood samples of 43 lung adenocarcinoma patients, who harbored EGFR mutations, and subsequently developed resistance to EGFR TKIs. We used BurningRock Biotech’s panels, consisting of critical exons and introns, covering multiple classes of somatic mutations, including single nucleotide variation (SNVs), rearrangements, copy number variations (CNVs) and insertions and deletions (INDELs) to detect genetic alterations both qualitatively and quantitatively.
    
    Results:
    We investigated the mutation spectrum after the development of resistance to EGFR-TKIs. Our analysis revealed 64% (18/28) of patients, harboring exon 19 deletions at baseline, acquired T790M at the time of progression. In contrast, only 33% (5/15) of patients, harboring exon 21 L858R substitutions at baseline, acquired T790M, indicating T790M mutation is more commonly found in patients with exon 19 deletions (p=0.052). Next, we associated T790M status with cumulative EGFR-TKI exposure time, and found patients had longer TKI exposure are more likely to acquire T790M mutation. The median TKI exposure time for patients who eventually acquired T790M was 19.20m ±1.86. In contrast, the median exposure time for patients who never acquired T790M 12.20m±1.20m (P =0.017). Furthermore, we investigated the presence of T790M mutation with progression free survival (PFS). Our data revealed that 68% (15/22) of patients with PFS≥12 months acquired T790M mutation after TKI exposure. In contrast, among patients with PFS< 12 months, only 38% of them acquired T790M mutation (p=0.048).
    
    Conclusion:
    Patients who eventually acquired T790M mutation have longer cumulative TKI exposure and are associated with longer PFS before the emergence of drug resistance. In addition, we also discovered that patients harboring exon 19 deletions are more likely to develop T790M mutation. Therefore, T790M status can be used as a potential biomarker for prognosis.