Unknown

Dataset Information

0

Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.


ABSTRACT: 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 .).

SUBMITTER: Drilon A 

PROVIDER: S-EPMC5857389 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.

Drilon Alexander A   Laetsch Theodore W TW   Kummar Shivaani S   DuBois Steven G SG   Lassen Ulrik N UN   Demetri George D GD   Nathenson Michael M   Doebele Robert C RC   Farago Anna F AF   Pappo Alberto S AS   Turpin Brian B   Dowlati Afshin A   Brose Marcia S MS   Mascarenhas Leo L   Federman Noah N   Berlin Jordan J   El-Deiry Wafik S WS   Baik Christina C   Deeken John J   Boni Valentina V   Nagasubramanian Ramamoorthy R   Taylor Matthew M   Rudzinski Erin R ER   Meric-Bernstam Funda F   Sohal Davendra P S DPS   Ma Patrick C PC   Raez Luis E LE   Hechtman Jaclyn F JF   Benayed Ryma R   Ladanyi Marc M   Tuch Brian B BB   Ebata Kevin K   Cruickshank Scott S   Ku Nora C NC   Cox Michael C MC   Hawkins Douglas S DS   Hong David S DS   Hyman David M DM  

The New England journal of medicine 20180201 8


<h4>Background</h4>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.<h4>Methods</h4>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  ...[more]

Similar Datasets

| S-EPMC7446323 | biostudies-literature
| S-EPMC5992878 | biostudies-literature
| S-EPMC6419506 | biostudies-literature
| S-EPMC8997457 | biostudies-literature
| S-EPMC6263791 | biostudies-literature
| S-EPMC8168097 | biostudies-literature
| S-EPMC7497841 | biostudies-literature
| 2200151 | ecrin-mdr-crc
| S-EPMC6847856 | biostudies-literature
| S-EPMC7651037 | biostudies-literature