Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

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 02 22
URL
Abstract Text 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.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.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.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 .).

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

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
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
NTRK1 A608D missense unknown NTRK1 A608D lies within the protein kinase domain of the Ntrk1 protein (UniProt.org). A608D has been demonstrated to promote secondary drug resistance in the context of CTRC-NTRK1 (PMID: 29466156), but has not been biochemically characterized and therefore, its effect on Ntrk1 protein function is unknown (PubMed, Jul 2022). Y
NTRK1 F589L missense unknown NTRK1 F589L lies within the protein kinase domain of the Ntrk1 protein (UniProt.org). F589L has been demonstrated to promote secondary drug resistance in the context of LMNA-NTRK1 (PMID: 29466156) and TMP3-NTRK1 (PMID: 33328556), but has not been biochemically characterized and therefore, its effect on Ntrk1 protein function is unknown (PubMed, Jul 2022). Y
NTRK1 G667S missense unknown NTRK1 G667S lies within the protein kinase domain of the Ntrk1 protein (UniProt.org). G667S has been associated with kinase inhibitor resistance in the context of NTRK1 fusion (PMID: 29466156, PMID: 33328556), but has not been biochemically characterized and therefore, its effect on Ntrk1 protein function is unknown (PubMed, Jul 2022). Y
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NTRK2 fusion Advanced Solid Tumor sensitive Larotrectinib FDA approved Actionable In three trials that supported FDA approval, Vitrakvi (larotrectinib) treatment resulted in an overall response rate of 75% (41/55) in adult and pediatric patients with advanced solid tumors harboring either an NTRK1, NTRK2, or NTRK3 fusion, including 7 patients achieving a complete response and 34 patients achieving a partial response (PMID: 29466156; NCT02122913, NCT02637687, NCT02576431). detail... 29466156
NTRK1 fusion pancreatic cancer predicted - sensitive Larotrectinib Case Reports/Case Series Actionable In a Phase I trial, Vitrakvi (larotrectinib) treatment resulted in partial response in a patient with pancreatic cancer harboring NTRK1 fusions (PMID: 29466156, Annals of Oncology, Volume 29, Issue suppl_5; NCT02122913, NCT02637687, and NCT02576431). 29466156 detail...
NTRK1 fusion appendix cancer predicted - sensitive Larotrectinib Case Reports/Case Series Actionable In a Phase I trial, Vitrakvi (larotrectinib) treatment resulted in stable disease in a patient with appendix cancer harboring NTRK1 fusions (PMID: 29466156, Annals of Oncology, Volume 29, Issue suppl_5; NCT02122913, NCT02637687, and NCT02576431). 29466156 detail...
NTRK1 fusion Advanced Solid Tumor sensitive Larotrectinib FDA approved Actionable In three trials that supported FDA approval, Vitrakvi (larotrectinib) treatment resulted in an overall response rate of 75% (41/55) in adult and pediatric patients with advanced solid tumors harboring either an NTRK1, NTRK2, or NTRK3 fusion, including 7 patients achieving a complete response and 34 patients achieving a partial response (PMID: 29466156; NCT02122913, NCT02637687, NCT02576431). detail... 29466156 detail...
NTRK1 fusion colon cancer sensitive Larotrectinib Case Reports/Case Series Actionable In a Phase I trial, Vitrakvi (larotrectinib) treatment resulted in partial response in 50% (2/4) and stable disease in 50% (2/4) of patients with colon cancer harboring NTRK1 fusions (PMID: 29466156, Annals of Oncology, Volume 29, Issue suppl_5; NCT02122913, NCT02637687, and NCT02576431). 29466156 detail...