TY - JOUR
T1 - Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma
AU - Waguespack, Steven G.
AU - Drilon, Alexander
AU - Lin, Jessica J.
AU - Brose, Marcia S.
AU - McDermott, Ray
AU - Almubarak, Mohammed
AU - Bauman, Jessica
AU - Casanova, Michela
AU - Krishnamurthy, Anuradha
AU - Kummar, Shivaani
AU - Leyvraz, Serge
AU - Oh, Do Youn
AU - Park, Keunchil
AU - Sohal, Davendra
AU - Sherman, Eric
AU - Norenberg, Ricarda
AU - Silvertown, Josh D.
AU - Brega, Nicoletta
AU - Hong, David S.
AU - Cabanillas, Maria E.
N1 - Funding Information:
The authors would like to thank the patients, their families, and all investigators involved in these studies. Medical writing support was provided by Anastasija Pesevska, PharmD and editorial support was provided by George Chappell, MSc, both of Scion, London, UK, supported by Bayer according to Good Publication Practice guidelines. The Sponsor was involved in the study design, collection, analysis, and interpretation of data, as well as data checking of information provided in the manuscript. However, ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors.
Publisher Copyright:
© 2022 The authors.
PY - 2022/6
Y1 - 2022/6
N2 - Objective: Larotrectinib is a highly selective tropomyosin receptor kinas e (TRK) inhibitor with demonstrated efficacy across various TRK fusion-positive solid tumours. We assessed t he efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma (TC). Methods: We pooled data from three phase I/II larotrectinib clinical trials (NCT02576431, NCT02122913, and NCT02637687). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints i ncluded duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Data cut-off: July 2020. Results: Twenty-nine patients (median age: 60; range: 6-80) with TRK fu sion-positive TC were treated. Tumour histology was papillary (PTC) in 20 (69%) patients, follicular (FTC) in 2 (7%), and anaplastic (ATC) in 7 (24%) patients. Among 28 evaluable patients, ORR was 71% (95% CI: 51-87); best responses were complete response in 2 (7%) patients, partial response in 18 (64%), stable disease in 4 (14%), progressive di sease in 3 (11%), and undetermined in 1 (4%) due to clinical progression prior to the first post-baseline assessment . ORR was 86% (95% CI: 64-97) for PTC/FTC and 29% (95% CI 4-71) for ATC. Median time to response was 1.87 months (range 1.64-3.68). The 24-month DoR, PFS, and OS rates were 81, 69, and 76%, respectively. Treatment-related adv erse events were mainly grades 1-2. Conclusion: In TRK fusion-positive TC, larotrectinib demonstrates rapid an d durable disease control and a favourable safety profile in patients with advanced disease requiring syste mic therapy.
AB - Objective: Larotrectinib is a highly selective tropomyosin receptor kinas e (TRK) inhibitor with demonstrated efficacy across various TRK fusion-positive solid tumours. We assessed t he efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma (TC). Methods: We pooled data from three phase I/II larotrectinib clinical trials (NCT02576431, NCT02122913, and NCT02637687). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints i ncluded duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Data cut-off: July 2020. Results: Twenty-nine patients (median age: 60; range: 6-80) with TRK fu sion-positive TC were treated. Tumour histology was papillary (PTC) in 20 (69%) patients, follicular (FTC) in 2 (7%), and anaplastic (ATC) in 7 (24%) patients. Among 28 evaluable patients, ORR was 71% (95% CI: 51-87); best responses were complete response in 2 (7%) patients, partial response in 18 (64%), stable disease in 4 (14%), progressive di sease in 3 (11%), and undetermined in 1 (4%) due to clinical progression prior to the first post-baseline assessment . ORR was 86% (95% CI: 64-97) for PTC/FTC and 29% (95% CI 4-71) for ATC. Median time to response was 1.87 months (range 1.64-3.68). The 24-month DoR, PFS, and OS rates were 81, 69, and 76%, respectively. Treatment-related adv erse events were mainly grades 1-2. Conclusion: In TRK fusion-positive TC, larotrectinib demonstrates rapid an d durable disease control and a favourable safety profile in patients with advanced disease requiring syste mic therapy.
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U2 - 10.1530/EJE-21-1259
DO - 10.1530/EJE-21-1259
M3 - Article
C2 - 35333737
AN - SCOPUS:85129781056
VL - 187
SP - 631
EP - 643
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 1
ER -