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Michael C. Cox

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-40 - Rapid, Robust and Durable Responses to Larotrectinib in Patients with TRK Fusion Non-Small Cell Lung Cancer (ID 14528)

      16:45 - 18:00  |  Author(s): Michael C. Cox

      • Abstract
      • Slides

      Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic independent of tumor lineage and are widely distributed across cancers. NTRK gene fusions were first reported in lung cancer in 2013 (Vaishnavi et al Nat Med 2013). Larotrectinib is a potent and highly selective oral tropomyosin receptor kinase (TRK) inhibitor in clinical development. Initial data of treatment of 55 patients with TRK fusion cancer resulted in an investigator-assessed objective response rate of 80%, and 71% of patients still in response at one year (Drilon et al., NEJM 2018). We report here on the safety and efficacy of larotrectinib in 4 patients with NSCLC from the 55 patient dataset.
      a9ded1e5ce5d75814730bb4caaf49419 Method
      Patients with previously treated lung adenocarcinoma were treated under clinical trial and enrolled based on a molecular report of NTRK gene fusion from a CLIA-certified lab. Larotrectinib was administered at 100 mg BID until disease progression or lack of clinical benefit. Tumors were assessed by investigators every 8 weeks using RECIST v1.1 criteria.
      4c3880bb027f159e801041b1021e88e8 Result

      As of July 17, 2017, four patients with adenocarcinoma of the lung who had progressed after 1 or more lines of platinum-based chemotherapy for advanced disease were enrolled. Three patients harbored an NTRK1 fusion and one an NTRK3 fusion. Three of 4 patients had a partial response or complete response confirmed on a subsequent scan. One patient with a possible brain metastasis demonstrated regression of mass on MRI. Responses were rapid and robust, with a time to response ranging between 49 and 56 days. At the time of analysis, 3 patients continued to have an ongoing response ranging between 5.7 and 12 months. The other patient had stable disease and progressed outside of the CNS after 300 days of treatment and continued on larotrectinib for clinical benefit. Larotrectinib was well tolerated, with 3 of 4 patients having grade 1 events only.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Larotrectinib treatment resulted in rapid and durable responses and had a well tolerated adverse event profile with no CNS progressive events in patients with previously treated lung cancer harboring NTRK gene fusions. These results strongly support the inclusion of NTRK gene fusions as part of routine testing for patients with lung cancer.


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