Efficacy of Larotrectinib inTRKFusion–Positive Cancers in Adults and Children
| العنوان: | Efficacy of Larotrectinib inTRKFusion–Positive Cancers in Adults and Children |
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| المؤلفون: | Steven G. DuBois, Michael J. Nathenson, John F. Deeken, Anna F. Farago, Luis E. Raez, Alberto S. Pappo, Ryma Benayed, Alexander Drilon, Funda Meric-Bernstam, Christina S. Baik, Brian B. Tuch, David M. Hyman, Valentina Boni, Noah Federman, Marcia S. Brose, Ulrik Lassen, Douglas S. Hawkins, Kevin Ebata, Nora Ku, Jordan Berlin, Scott Cruickshank, Leo Mascarenhas, Theodore W. Laetsch, Brian Turpin, George D. Demetri, Afshin Dowlati, Patrick C. Ma, Shivaani Kummar, David S. Hong, Robert C. Doebele, Jaclyn F. Hechtman, Ramamoorthy Nagasubramanian, Davendra Sohal, Matthew H. Taylor, Michael C. Cox, Wafik S. El-Deiry, Marc Ladanyi, Erin R. Rudzinski |
| المصدر: | The New England journal of medicine, vol 378, iss 8 |
| بيانات النشر: | Massachusetts Medical Society, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, Oncogene Proteins, Fusion, Phases of clinical research, Entrectinib, Kaplan-Meier Estimate, Medical and Health Sciences, 0302 clinical medicine, Overall response rate, Neoplasms, Clinical endpoint, Young adult, Child, Cancer, Oncogene Proteins, Pediatric, General Medicine, Middle Aged, Highly selective, Editorial Commentary, Child, Preschool, 6.1 Pharmaceuticals, 030220 oncology & carcinogenesis, Female, Patient Safety, Adult, medicine.medical_specialty, Adolescent, Antineoplastic Agents, Disease-Free Survival, Young Adult, 03 medical and health sciences, Clinical Research, General & Internal Medicine, Internal medicine, medicine, Humans, Fusion, Preschool, Aged, business.industry, Receptor Protein-Tyrosine Kinases, Infant, Evaluation of treatments and therapeutic interventions, Clinical trial, Pyrimidines, 030104 developmental biology, Trk receptor, Pyrazoles, business, Protein Kinases |
| الوصف: | BackgroundFusions 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.MethodsWe 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.ResultsA 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.ConclusionsLarotrectinib 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 .). |
| وصف الملف: | application/pdf |
| تدمد: | 1533-4406 0028-4793 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8038e7eee9bf93284d85c198521865a4Test https://doi.org/10.1056/nejmoa1714448Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8038e7eee9bf93284d85c198521865a4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15334406 00284793 |
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