Novel pan-TRK inhibitor larotrectinib shows durable efficacy in patients with TRK fusion-positive tumors


Fusion genes of the NTRK1, NTRK2, or NTRK3 genes (encoding the TRKA, TRKB or TRKC receptor tyrosine kinases) are rare but could occur across multiple types of cancers. This mutation leads to ligand-independent constitutive kinase activity, activating growth and survival signaling pathways in cancer cells. Larotrectinib is a novel pan-TRK inhibitor currently under development. This study analyzes two phase I trials and one phase II trial of patients at different ages (adult, adolescent and pediatric). 55 patients with 13 discrete cancer types with TRK fusions are included: salivary (12), sarcoma (10), infantile fibrosarcoma (7), lung (5), thyroid (5), colon (4), melanoma (4), cholangio (2), GIST (2), and other (4). Among 46 patients with confirmatory response data, the objective response rate (ORR) was 78% and 13% had a complete response (CR). At the time of analysis, the longest responder remained treated for 23 months and the median progression-free survival was not reached. The most common treatment-related adverse events were grade 1 or 2, including dizziness (20%), fatigue (18%) and nausea (18%). These results show larotrectinib has durable antitumor activity in TRK fusion cancers.

Hyman DM, et al., J Clin Oncol 35, 2017 (suppl; abstr LBA2501)

doi: 10.1093/annonc/mdx155

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