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Marcos André Costa



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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: 2
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.13-13 - Afatinib in Lung Adenocarcinoma Harboring de novo EGFR Exon 20 Insertions. (ID 14029)

      12:00 - 13:30  |  Presenting Author(s): Marcos André Costa

      • 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 1st-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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      P3.13-27 - Clinical Outcomes of Patients with Lung Adenocarcinoma Harboring Concomitant Driver Mutations in a Brazilian Cancer Center (ID 13959)

      12:00 - 13:30  |  Presenting Author(s): Marcos André Costa

      • Abstract

      Background

      NSCLC, particularly adenocarcinoma, has been successfully treated with upfront targeted therapies according to respective oncogenic mutations in a tailor-made model. It has led to improvement in clinical outcomes (CO) and QoL, however, some evidences sugest that the occurrence of concomitant driver mutations (OCDM) is responsible for poorer results than expected. Questions, thus, have emerged regarding the best strategy to this population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this retrospective study, we reviewed lung cancer patients treated in our institution in the last four years in order to identify the OCDM. The vast majority of patients performed Next Generation Sequencing (NGS) using Illumina HiSeqs of Foundation Medicine (FM). The f/u was obtained from our electronic charts.

      4c3880bb027f159e801041b1021e88e8 Result

      From apr/14 to apr/18, 5 patients were elegible for this analysis, 2M / 3F, mean 59y/o. Patient 1: treated with crizotinib because of MET amplification harboring concomitantly ATM deletion exons 11-50. Died after pneumonia before first radiologic evaluation. Patient 2: osimertinib for EGFR T790M harboring BRCA-2 c1528G>T. Derived partial response (PR) with PD after 9 mo. Patient 3: immunotherapy because of TMB 18 + PD-L1 e PD-L2 amplification, harboring STK11 Q159fs*2 as well. Curiously, the previous report of PD-L1 (22C3) by IHC had been negative. Still in PR, lasting 14 mo. Germline analysis (to Peutz-Jeghers) will soon be performed. By FM, Everolimus or Temsirolimus were sugested. Patient 4: crizotinib and alectinib for ALK-EML4 fusion harboring concomitantly BRCA2 S1074R. Had PR lasting 9 mo and only 6 mo respectively. Curiously, previous FISH had not identified the translocation. Patient 5: treated with crizotinib because of ALK-EMLA4 translocation harboring concomitantly Kras mutation. This is a rare condition and, until recently, de novo rearrangements of ALK was thought to be mutually exclusive to Kras. Not surprisingly, and in line with some reports of literature, the patient experienced rapid progression, saw already in the first control in 8 weeks.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study confirms that the OCDM has been increasingly seen due to the employment of improved sensitivity genetic techniques, like NGS. Additionally, provides the clinical outcomes of patients with lung adenocarcinoma harboring more than one of those mutations, which is broadly unknown yet. Finally, previous reports account that, particularly, patients with concomitant ALK fusion and Kras mutation carry poorer results with anti-ALK than expected. This study reinforces this observation and argues that the best management of these patents is still to be clarified.

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