Activity of larotrectinib in TRK fusion cancer patients with brain metastases or primary central nervous system tumors
| Autor: | Steven G. DuBois, Anna F. Farago, Birgit Geoerger, Juneko E. Grilley-Olson, Nora Ku, Shivani Nanda, Davendra Sohal, David S. Hong, Alexander Drilon, Barrett H. Childs, David S. Ziegler, Cornelis M. van Tilburg, Francois P. Doz, Michael C. Cox |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 37:2006-2006 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 2006 Background: TRK fusions are oncogenic drivers of a variety of cancers, 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). While larotrectinib has been shown to cross the blood–brain barrier (Ziegler et al, Br J Cancer 2018), its clinical activity in a series of TRK fusion cancers with primary or metastatic intracranial disease has not been described. Methods: Patients (pts) with non-primary CNS solid tumors with brain metastases, or primary CNS tumors harboring a TRK fusion treated with larotrectinib in 2 clinical trials (NCT02637687, NCT02576431) were identified. Larotrectinib was administered until disease progression (PD), withdrawal, or unacceptable toxicity. Disease status was investigator-assessed (RANO and RECIST). Data cutoff: July 30, 2018. Results: 14 pts were identified: 5 non-primary CNS solid tumors (3 lung cancer, 2 thyroid cancer; fusion type: 2 ETV6-NTRK3, 2 SQSTM1-NTRK3, 1 EPS15-NTRK1; age range 25–79 y) and 9 primary CNS tumors (3 glioma, 2 glioblastoma, 1 astrocytoma, 3 NOS; fusion type: 3 BCR-NTRK2, 2 KANK-NTRK2, 1 each of AFAP1-NTRK1, AGTPBP1-NTRK2, ETV6-NTRK3, SPECC1L-NTRK2; age range 2–79 y). In the 5 pts with non-primary CNS tumors, the best objective response to therapy was PR in 3 (60%, 1 pending confirmation), SD in 1 (20%), and not evaluable (NE) in 1 (20%). Duration of response ranged from 9+ to 13 mo. In the 9 pts with primary CNS tumors, disease control was achieved in all evaluable pts (primary PD not observed; 1 pt required dose increase). The best objective response to therapy was PR in 1 (11%; pending confirmation, −55% tumor shrinkage, ongoing at 3.7 mo), SD in 7 (78%; tumor shrinkage range −1% to −24% for pts with measurable disease, 5 had SD > 4 mo), and NE in 1 (11%). Duration of treatment ranged from 2.8–9.2+ mo. Conclusions: Larotrectinib is active in pts with TRK fusion cancers with intracranial disease. Confirmed responses and durable disease control were seen in metastatic disease and primary CNS tumors of various histologies. These results further support expanded testing for TRK fusions across all cancers, including primary CNS tumors. Clinical trial information: NCT02637687 and NCT02576431. |
| Databáze: | OpenAIRE |
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