Author of

• 10743

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  P1.10 - Poster Session 1 - Chemotherapy (ID 204)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10762

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    P1.10-019 - Differential efficacy of EGFR-TKI according to variants of exon 19 deletional mutation in non-small cell lung cancer (ID 1177)

    09:30 - 09:30  |  Author(s): R. Kaji
    • Abstract

    Background
    Deletional mutations in exon 19 (Del-19) and L858R point mutation in exon 21 are the most common mutations in the epidermal growth factor receptor (EGFR) gene. In Del-19, several variants actually exist, consisting of different amino acid positions or different sizes. Little evidence has been described whether the variation of Del-19 mutation affects EGFR-tyrosine kinase inhibitor (TKI) sensitivity.

    Methods
    Between December 2005 and March 2013, we screened 111 patients harboring Del-19 who had received EGFR-TKIs. Efficacies of EGFR-TKI such as response rate (RR), progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated among various patient characteristics (age, gender, ECOG performance status [PS], smoking status, clinical stage, histology, treatment line, types of TKI, initial site of deletion, and presence of insertion). We also performed a multivariate analysis with the proportional hazards model to exclude several confounds. A backward stepwise approach was adopted as our variable selection method for multivariate analyses.

    Results
    Among these 111 patients with exon 19 deletion mutations, 83 (75%) patients had a deletion from E746 (⊿E746 group), and a deletion from L747 (⊿L747 group) 28 (25%). PFS of ⊿E746 group (12.0 months, 95% confidence interval [CI] 9.27-15.63) was significantly longer than ⊿L747 group (10.0 months, 95% CI 6.43-14.27) (p = 0.0129). Insertion mutations were found in 20 patients (18%), and 91 patients (82%) were without insertions. PFS without insertions (12.0 months, 95% CI 9.27-15.17) was significantly longer than with insertions (10.0 months, 95% CI 3.97-12.67) (p = 0.0173). No relationships were found for RR in all patient characteristics. In univariate analysis, PS (0-1 vs 2-4, p = 0.0001), clinical stage (ⅢB/Ⅳ vs recurrence, p = 0.0408), treatment line (1st line vs after 2nd line, p = 0.0122), initial site of deletion, and presence of insertion were statistically significant factors for longer PFS. PS (p <0.0001), histology (Adeno vs Squamous, p = 0.0134) and treatment line (p = 0.0052) were statistically significant factors for longer OS. In multivariate analysis, PS (hazards ratio [HR] 0.580, 95% CI 0.43-0.80, p = 0.0009) and initial site of deletion (HR 0.696, 95% CI 0.55-0.89, p = 0.0047) remained as significant factors for longer PFS. PS (HR 0.525, 95% CI 0.35-0.78, p = 0.0016), gender (Female vs Male, HR 0.701, 95% CI 0.53-0.93, p = 0.0140) and histology (HR 0.479, 95% CI 0.30-0.83, p = 0.0120) were selected as significant factors for longer OS.

    Conclusion
    Our data indicated better efficacy of EGFR-TKI in ⊿E746 group than ⊿L747 group. Deletional locations may affect the sensitivity to EGFR-TKI.