Author of

• 25520

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  Poster Display session (Friday) (ID 65)

  • Event: ELCC 2018
  • Type: Poster Display session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1

  • 25360

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    159P - Clinical activity of afatinib in a cohort of patients with lung adenocarcinoma harbouring uncommon EGFR mutations: A Spanish retrospective multicentre study (ID 269)

    12:50 - 12:50  |  Author(s): R. Palmero
    • Abstract

    Background:
    Uncommon EGFR mutations (u-EGFRm) in exons 18–21 account for 12–15% of overall EGFR mutations in non-small cell lung cancer (NSCLC). Afatinib has shown activity against some u-EGFRm, especially G719X, L861Q, and S768I; although other u-EGFRm (Ins20, de novo T790M) have a lower likelihood of response. U-EGFRm are a heterogeneous group of molecular alterations and have also been reported as co-mutations with other EGFR mutations (complex mutations). We examined the molecular and clinical characteristics and efficacy of afatinib in a cohort of patients with advanced NSCLC patients carrying u-EGFRm in Spanish clinical practice.
    
    Methods:
    Medical records of 67 NSCLC patients with u-EGFRm treated with afatinib between 2012 and 2017 at 23 Spanish institutions were reviewed. U-EGFRm were analysed as complex mutations (Group A), Ins20 (Group B), or single mutations (Group C). Efficacy data were evaluated in terms of tumour response and overall survival (OS).
    
    Results:
    Of the 67 patients, 96% were Caucasian, all were adenocarcinoma, 46% were never smokers and 37% were former smokers, 79% were Stage IV at diagnosis, 79% had ECOG PS 0–1. Group A complex u-EGFRm consisted of double mutations of G719X + E709F, G719X + S768I, G719X + L861Q, L858R + T790M, L858R + S768I, Del19 + S768I, Del19 + L747S, or R776C + L861Q. No differences in clinical characteristics were found between Group A (n = 20), Group B (n = 23), and Group C (n = 24). Afatinib was administered as 1st line therapy in 80% of patients. Median time on therapy was 4.2 months (range 2.0–12.9). Eighteen percent of patients started afatinib at a reduced dose and 24% of patients required a dose reduction. Response to afatinib was significantly higher in Group A and C (70% and 54%, respectively), compared with Group B (13%; pairwise comparison p < 0.001 and 0.013, respectively, Table). Median OS (mOS) for the entire cohort was 19.9 months (9.7–30.1). Hazard ratio for OS were 0.27 (95% CI 0.10-0-71; p = 0.009) and 0.40 (95% CI 0.17–0.95; p = 0.037) for Group A and C compared to Group B, respectively.

    u-EGFRm	Group A (complex)n = 20	Group B (Ins20)n = 23	Group C (other)n = 24
    Response to afatinib, n (%)
    Complete response	1 (5.0)	0 (0)	1 (4.2)
    Partial response	13 (65.0)	3 (13.0)	12 (50.0)
    Stable disease	3 (15.0)	8 (34.8)	5 (20.8)
    Progressive disease	0 (0)	10 (43.5)	3 (12.5)
    Not evaluable	3 (15.0)	2 (8.7)	3 (12.5)
    mOS (95% CI), months	28.8 (20.7–36.8)	10.7 (6.2–15.3)	19.9 (10.8–29.0)
    	p = 0.014

    
    
    Conclusions:
    In clinical practice, afatinib was active in u-EGFRm NSCLC, particularly in complex and single mutations. Further strategies are needed for patients with ins20, a subgroup u-EGFRm with a lower clinical benefit from afatinib.
    
    Clinical trial identification:
    
    
    Legal entity responsible for the study:
    Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
    
    Funding:
    Has not received any funding
    
    Disclosure:
    All authors have declared no conflicts of interest.