Reference Detail

Ref Type Journal Article
PMID (29466156)
Authors Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, Nathenson M, Doebele RC, Farago AF, Pappo AS, Turpin B, Dowlati A, Brose MS, Mascarenhas L, Federman N, Berlin J, El-Deiry WS, Baik C, Deeken J, Boni V, Nagasubramanian R, Taylor M, Rudzinski ER, Meric-Bernstam F, Sohal DPS, Ma PC, Raez LE, Hechtman JF, Benayed R, Ladanyi M, Tuch BB, Ebata K, Cruickshank S, Ku NC, Cox MC, Hawkins DS, Hong DS, Hyman DM
Title Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.
Journal The New England journal of medicine
Vol 378
Issue 8
Date 2018 Feb 22
URL
Abstract Text Background Fusions involving one of three tropomyosin receptor kinases (TRK) occur in diverse cancers in children and adults. We evaluated the efficacy and safety of larotrectinib, a highly selective TRK inhibitor, in adults and children who had tumors with these fusions. Methods We enrolled patients with consecutively and prospectively identified TRK fusion-positive cancers, detected by molecular profiling as routinely performed at each site, into one of three protocols: a phase 1 study involving adults, a phase 1-2 study involving children, or a phase 2 study involving adolescents and adults. The primary end point for the combined analysis was the overall response rate according to independent review. Secondary end points included duration of response, progression-free survival, and safety. Results A total of 55 patients, ranging in age from 4 months to 76 years, were enrolled and treated. Patients had 17 unique TRK fusion-positive tumor types. The overall response rate was 75% (95% confidence interval [CI], 61 to 85) according to independent review and 80% (95% CI, 67 to 90) according to investigator assessment. At 1 year, 71% of the responses were ongoing and 55% of the patients remained progression-free. The median duration of response and progression-free survival had not been reached. At a median follow-up of 9.4 months, 86% of the patients with a response (38 of 44 patients) were continuing treatment or had undergone surgery that was intended to be curative. Adverse events were predominantly of grade 1, and no adverse event of grade 3 or 4 that was considered by the investigators to be related to larotrectinib occurred in more than 5% of patients. No patient discontinued larotrectinib owing to drug-related adverse events. Conclusions Larotrectinib had marked and durable antitumor activity in patients with TRK fusion-positive cancer, regardless of the age of the patient or of the tumor type. (Funded by Loxo Oncology and others; ClinicalTrials.gov numbers, NCT02122913 , NCT02637687 , and NCT02576431 .).

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Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ETV6-NTRK3 gastrointestinal stromal tumor predicted - sensitive Larotrectinib Phase I Actionable In a Phase I trial, Vitrakvi (larotrectinib) treatment resulted in complete response in 1 and partial response in 2 patients with gastrointestinal stromal tumor harboring ETV6-NTRK3 fusions (PMID: 29466156, Annals of Oncology, Volume 29, Issue suppl_5; NCT02122913, NCT02637687, and NCT02576431). 29466156 detail...
ETV6-NTRK3 Advanced Solid Tumor sensitive Larotrectinib Phase II Actionable In a combined analysis of three trials, Vitrakvi (larotrectinib) treatment resulted in complete response in 21.4% (6/28) and partial response in 67.9% (19/28) of patients with advanced solid tumors harboring an ETV6-NTRK3 fusion (PMID: 29466156; NCT02122913, NCT02637687, NCT02576431). 29466156