Author of

• 25967

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  P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

  • 27673

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    P3.13-13 - Afatinib in Lung Adenocarcinoma Harboring de novo EGFR Exon 20 Insertions. (ID 14029)

    12:00 - 13:30  |  Author(s): Jairo Lewgoy
    • Abstract

    Background
    

    NSCLC, particularly adenocarcinoma, has been successfully treated with upfront targeted therapies according to respective oncogenic mutations in a tailor-made model. EGFR-TK inhibitors (TKi) have exhibited major responses, improving PFS, RR and even mOS (a subset treated with afatinib). This drug has emerged as the best option for those with uncommon mutations, but until now is broadly unknown its action in exon 20 mutations, which accounts for nearly 3% of all and, classically, is associated to worse response to 1^st-generation TKi.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Here, in this retrospective analysis, is reported the past medical history and clinical outcomes of two patients who presented with de novo EGFR exon 20 insertions: D770_N771insSVD and Ser768_Asp770dup. The patient were treated in two differents Cancer Centers in Brazil and the mutations were identified with Next Generation Sequencing (NGS) by Illumina HiSeqs of Foundation Medicine (FM) and the other by a local certified laboratory using Ion Torrent-PGM Thermo Fischer v5.0. Analysis were performed in tissue samples extracted from FFPE. The follow-up was obtained from electronic charts.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Patient 1: never-smoker 66 y/o lady, without comorbidities, presented 12 mo ago with dry cough, thoracic pain and -10% of weight. CT scan revealed extensive ground-glass infiltration area and multiple bilateral pulmonary nodules. Lung biopsy pointed out a mod. differentiated adenocarcinoma of predominantly lepidic pattern (IHC: AE1/2+, CK20-, CK7+, Napsin A+, TTF1+). With this, rtPCR (Cobas Mu test v.2) detected an exon 20 insertion, thus ineligible to upfront EGFR-TKi. However, was chosen to re-analyze it using NGS (FM). After a TAT of only 2 weeks, we retrieved the result which showed a poorly described mutation: EGFR exon 20 insertion D770_N771insSVD. Afatinib 30mg/day was started and, only three days after the initiation, the patient decreased the dry cough and fatigue. CT scans showed stable disease after 45 days of continuous use. Patient 2 had a more extensive past medical history: 1L chemo, followed by nivolumab and docetaxel. Lastly, NGS revealed an uncommon EGFR exon 20 insertion (Ser768_Asp770dup). Rapid clinical improvement was observed (less fatigue and dyspneia), but occured liver progression in the first control, 4w after initiation.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    This study confirms that rare mutations have been increasingly seen due to the employment of improved sensitivity genetic techniques, like NGS. Furthermore, reveals two rare examples of rapid clinical response to afatinib in patients harboring EGFR exon 20 insertions. Finally, despite it could be an option for management of this broadly unknown situation, it suggests caution because of the short-lasting benefit in some.

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