Activity of larotrectinib in TRK fusion cancer patients with primary central nervous system tumours
| Autor: | Steven G. DuBois, A. Drilon, Shivani Nanda, C.M. van Tilburg, Antoine Italiano, Michael Capra, Andrej Lissat, David S. Hong, David S. Ziegler, J.-H. Kang, Birgit Geoerger, Ariadna Holynskyj, David M. Hyman, Valentina Boni, François Doz, Makoto Tahara, Sébastien Perreault, Juneko E. Grilley-Olson, N. Brega |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Disease status business.industry Central nervous system Cancer Hematology Disease medicine.disease Clinical trial Fusion gene 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis Internal medicine Trk receptor medicine Until Disease Progression business |
| Zdroj: | Annals of Oncology. 30:ix124 |
| ISSN: | 0923-7534 |
| Popis: | Background TRK fusions are oncogenic drivers of a variety of tumors, many of which can involve the central nervous system (CNS). Larotrectinib is an FDA-approved selective TRK inhibitor for the treatment of TRK fusion cancer (Drilon et al., NEJM 2018). Here we report on the clinical activity of larotrectinib in an expanded set of TRK fusion-positive primary CNS tumors. Methods Patients with primary CNS tumors harboring an NTRK gene fusion detected by local molecular testing who were treated with larotrectinib in two clinical trials (NCT02637687 and NCT02576431) were identified. Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was investigator assessed (RANO). Data cutoff: February 19, 2019. Results 18 patients with various histological types of glial tumors (11 high grade, 4 low grade, 3 unknown) were identified. The patients had gene fusions involving NTRK2 (n = 13), NTRK1 (n = 3) and NTRK3 (n = 2). Median age was 10.5 years (range 1.3–79.0); 14 patients were pediatric ( Conclusions Larotrectinib is active in patients with TRK fusion cancer with intracranial disease. Objective responses and durable disease control were seen in primary CNS tumors of various grades and histologies. These results further support expanded testing for NTRK gene fusions in patients with primary CNS tumors. Clinical trial identification NCT02637687 and NCT02576431. Legal entity responsible for the study Bayer. Funding Bayer. Disclosure All authors have declared no conflicts of interest. |
| Databáze: | OpenAIRE |
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