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Jacques Tabacoff



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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
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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  |  Author(s): Jacques Tabacoff

      • 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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