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M. Sereno Moyano

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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
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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)

      12:30 - 13:00  |  Author(s): M. Sereno Moyano

      • Abstract

      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.

      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).

      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-EGFRmGroup A (complex)n = 20Group B (Ins20)n = 23Group C (other)n = 24
      Response to afatinib, n (%)
      Complete response1 (5.0)0 (0)1 (4.2)
      Partial response13 (65.0)3 (13.0)12 (50.0)
      Stable disease3 (15.0)8 (34.8)5 (20.8)
      Progressive disease0 (0)10 (43.5)3 (12.5)
      Not evaluable3 (15.0)2 (8.7)3 (12.5)
      mOS (95% CI), months28.8 (20.7–36.8)10.7 (6.2–15.3)19.9 (10.8–29.0)
      p = 0.014

      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

      Has not received any funding

      All authors have declared no conflicts of interest.