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Artur Katz



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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-67 - Metastatic RET-Rearranged Lung Adenocarcinomas Treated with Alectinib: Retrospective Analysis of a Single Institution (Now Available) (ID 745)

      10:15 - 18:15  |  Author(s): Artur Katz

      • Abstract
      • Slides

      Background

      RET-rearrangements are well-described drivers in lung adenocarcinomas (LADC), identified in nearly 1-2% of the tumors, for which there are no current specific targeted therapies approved. Although several tyrosine-kinase inhibitors (TKI) (e.g vandetanib, cabozantinib, lenvatinib, etc) demonstrate anti-RET activity, poor tolerability and overall response rates less than 50% has been limiting its widespread adoption. The structural homology between the kinase domains of ALK and RET, as well as the documented in vitroactivity, and well-known toxicity profile makes alectinib an attractive drug for evaluation in clinical trials and, possibly, for off-label use in the setting of progression upon pemetrexed-based chemotherapy.

      Method

      Retrospective assessment of the clinical and molecular characteristics, drug efficacy and tolerability of RET-rearranged LADC patients treated with alectinib in a single institution.

      Result

      Among the four patients identified, 100% were white, female and non-smokers, between 59-66 years old; 2/4 presented with high carcinoembryonic antigen levels and 1/4 with poorly differentiated LADC. All patients were TKI naïve and underwent evaluation with FoundationOne® next-generation sequencing platform, which showed KIF5B-RETfusion in 3/4 (75%) and CCDC6-RETin 1/4 (25%) of the cases. Among other alterations shared, 3/4 (75%) presented with CDKN2A/Bloss; in all cases, the tumors were microssatelite stable (MSS) and had low tumor mutational burden (1-9 muts/Mb). All patients were treated with 600 mg bid of alectinib. Among the four patients assessed, one was not available for radiological response evaluation and the drug was withheld within two months of treatment due to clinical deterioration. The best ORR was partial response in 2/4 (50%), with PFS ranging from 4-5 months. In one patient, after 5 months of therapy, an asymptomatic oligoprogression in soft-tissue was observed; the patient was treated with local radiation therapy and remains on alectinib for 12 months. No grade 3/4 adverse events, dose reductions or discontinuation due to toxicity were observed.

      Conclusion

      Although this is a small single center evaluation, alectinib demonstrated clinical activity in RET-rearranged LADC, apart from being a well-tolerated treatment. Nevertheless, the concurrent molecular alterations, its prognostic significance, the ideal dosing regimen and the precise magnitude of benefit are all questions to be addressed in clinical trials, in order to consider alectinib a treatment option for this small subset of patients.

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      P2.14-68 - Dramatical Intracranial Response to Osimertinib in Patient Harbouring the Uncommum EGFR G719S/L861Q Mutation (Now Available) (ID 861)

      10:15 - 18:15  |  Author(s): Artur Katz

      • Abstract
      • Slides

      Background

      Almost 10% of EGFR mutations are represented by uncommom mutations, which represents a heterogenous group of rare molecular alterations, where the presence of co-mutations are even more rarely seen. Third generation shows efficacy and safety in these patients (Pt).

      Method

      We hereby report a case of dramatic intracranial response to osimertinib in a poor performance status Pt with lung cancer harbouring the uncommom epidermal growth factor receptor (EGFR) co-mutations encoded in exon 18 (G719S) and exon 21 (L861Q). The Pt was a 76-year-old male, smoker (60 packs-year), who visited our hospital with a prior history of 2-weeks mental confusion and seizures. Computed tomography detected several brain lesions with moderate edema, as well as lung, cervical and mediastinal lymphadenopathy, liver, adrenal and bone lesions. A biopsy specimen obtained from his cervical adenopaHty suggested primary stage IVB lung cancer with sarcomatoid differentiation (T2a N2 M1c) and PDL-1 expression of 10%. A MRI-brain was not performed due to the Pt altered mental status and also because his condition prevent the use of sedation. Due to the dramatic nature of the case and a very poor clinical condition, systemic treatment with carboplatin, paclitaxel and pembrolizumab was started while we waited for the results of NGS. There was no clinical evidence of response to this treatment. Just prior to the schedule day of the second cycle of chemotherapy we had access to the NGS result, which disclosed the presence of EGFR G719S (allele frequency of 49.7%) and L861Q (allele frequency of 50.8%).

      Result

      Based on recent reported data we started osimertinib 80mg/day. He had unequivocal clinical improvement over the following weeks with relieve of neurologic symptoms. After 42 days of treatment restaging PET-CT demonstrated complete response and brain MRI with remarkable response. Osimertinib has been well-tolerated for the Pt.

      Before and after 6w of osimertinib

      captura de tela 2019-04-10 às 21.19.21.png

      Conclusion

      This case report corroborates the promising activity of osimertinib in uncommom EGFR mutation. We have described the first case showing dramatic cranial response in these rare EGFR co-mutations.

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