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A. Gomez Rueda



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 2
    • 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): A. Gomez Rueda

      • 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-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


      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.

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      209P - The management of brain disease (BD) in ALK-rearranged non-small cell lung cancer (ALK NSCLC): Can systemic treatment delay the initiation of local treatments? Experience of the Ramón y Cajal University Hospital (RyCUH, Madrid) (ID 625)

      12:30 - 13:00  |  Author(s): A. Gomez Rueda

      • Abstract
      • Slides

      Background:
      The arrival of oral tyrosine kinase inhibitors (TKI) to the treatment of ALK NSCLC is becoming a paradigm shift in the treatment of BD (brain metastases and meningeal carcinomatosis), given the intracranial activity thereof, with the possibility of delaying the start of local treatments, as radiotherapy (RT), radiosurgery or neurosurgery, and the comorbidity that they entail.

      Methods:
      Between October 2013 and October 2017 were registered patients diagnosed with ALK NSCLC at the RyCUH. Patients with BD were considered eligible, well at diagnostic of the primary tumor, well at progression of it. The systemic treatment carried out is collected as well as the local treatment at diagnosis of the BD if this is done. We studied systemic (PFSs) and brain progression free survival (PFSb) as well as overall survival (OS) according to the type of treatment and moment received. Other variables were included as neurological symptomatology and corticotherapy.

      Results:
      Of the 33 patients diagnosed of ALK NSCLC, 42.42% had BD at some point of their evolution (57.14% at diagnosis and 42.86% at progression). As a first-line systemic treatment, 57.14% received chemotherapy and 42.85% received a TKI, although 71.43% received a TKI as a second-line treatment. 57.14% of the patients received whole radiation therapy and 28.57% radiosurgery at some point during their evolution. PFSb is higher in those patients without brain metastases at diagnosis, who initiate systemic treatment, and who perform local treatment at brain progression (14 months), compared to patients who change systemic treatment for brain progression (12 months). The median OS is higher in patients who do not initially receive local treatment (25.5 months) versus those who do (21 months).

      Conclusions:
      There are multiple strategies in the management of ALK NSCLC BD. Systemic treatment with TKIs allows to delay local treatment with RT or surgery and comorbidity. However, the use of RT or surgery for exclusive brain progression with controlled systemic disease allows the maintenance of TKI and prolong the PFSs.

      Clinical trial identification:


      Legal entity responsible for the study:
      Hospital Universitario Ramón y Cajal (Madrid)

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.

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