@article{9aa3df93f0a442759fb6e32695de0152,
title = "Comparative Effectiveness of Larotrectinib and Entrectinib for TRK Fusion Cancer",
abstract = "Larotrectinib and entrectinib are tumor-agnostic tropomyosin receptor kinase (TRK) inhibitors that are indicated for the treatment of advanced or metastatic solid tumor cancers with neurotrophic tyrosine receptor kinase (NTRK) gene fusions. Regulatory approval of both agents was based on data from single-arm phase 1/2 studies, including tumor-agnostic basket trials. In the absence of randomized controlled trials, there remains a paucity of data to demonstrate the comparative effectiveness of larotrectinib and entrectinib vs established standard-of-care treatments in cancers with NTRK gene fusions. Furthermore, no studies have directly compared the 2 agents. This article reviews what is known about the comparative effectiveness of larotrectinib and entrectinib vs standard therapies in TRK fusion cancer and examines the comparative effectiveness of the 2 TRK inhibitors. Historical and intrapatient comparisons suggest that TRK inhibitors improve disease response compared with preexisting treatments across most tumor histologies; indirect and limited comparisons of phase 1/2 data and preliminary simulation modeling suggest a potential advantage for larotrectinib over entrectinib in terms of clinical response and survival. Although limited, these data provide some insight into the position of these treatments in established treatment paradigms for TRK fusion cancer, a setting where real-world evidence will be slow to accrue due to the rare nature of these tumors but may be the only way in the future to answer the outstanding questions regarding these 2 agents. Meanwhile, we need to try to obtain the maximum benefit that can be achieved for our patients using the currently available knowledge.",
author = "Carlson, {Josh J.} and Antoine Italiano and Brose, {Marcia S.} and Noah Federman and Ulrik Lassen and Shivaani Kummar and Sullivan, {Sean D.}",
note = "Funding Information: Author disclosures: Dr Brose, Dr Carlson, Dr Federman, Dr Kummar, Dr Lassen, and Dr Sullivan have been part of consultancies or paid advisory boards with Bayer. Dr Brose and Dr Federman have been part of consultancies or paid advisory boards with Loxo Oncology. Dr Brose has also been part of consultancies or paid advisory boards with Genentech, AstraZeneca, and Eli Lilly and Company. Dr Brose has received honoraria from Clinical Care Options, Medscape, Onclive{\textregistered}, and PeerView. Dr Brose has also disclosed that research support to the University of Pennsylvania School of Pharmacy has been provided by Bayer, Loxo Oncology, Genentech, Eisai, Blueprint Medicines, Eli Lilly and Company, and Novartis. Dr Carlson has received honoraria from Adaptive Biotechnologies. Dr Federman has received lecture fees for speaking at the invitation of Bayer and received patent royalties from NanoValent Pharmaceuticals, Inc. Dr Federman has also disclosed that he holds stock in the for-profit health care companies Genmab, Reata Pharmaceuticals, and bluebird bio, Inc. Dr Italiano and Dr Lassen have both received grants from Roche. Dr Italiano has also received grants from AstraZeneca, Bayer, Merck, Merck Sharp & Dohme, and PharmaMar. Dr Italiano has disclosed that he has received honoraria from Bayer, Daiichi Sankyo, Epizyme, Ipsen, Roche, and SpringWorks Therapeutics. Dr Kummar has been part of consultancies or paid advisory boards with Boehringer Ingelheim, SpringWorks Therapeutics, Gilead, EcoR1 Capital, Seagen, Mundipharma, Mirati Therapeutics, Genome & Company, and Harbour Biomed. Dr Kummar has also disclosed that she is the cofounder and is an equity holder for PathomIQ. Dr Kummar has also disclosed that she is the editor-in-chief of Current Problems in Cancer (Elsevier) and that her spouse is a scientific adviser for Cadila Pharmaceuticals Ltd and is the founder of Arxeon Inc. Dr Lassen has also reported that he has been part of consultancies or paid advisory boards with Pfizer and Novartis. Dr Lassen has also received grants from Bristol Myers Squibb, GlaxoSmithKline, and Pfizer. Funding Information: Funding source: This article was published as part of a supplement that was financially supported by Bayer HealthCare Pharmaceuticals, Inc. Noah Federman{\textquoteright}s research is supported by NIH National Center for Advancing Translational Science (NCATS) UCLA Clinical & Translational Science Institute (CTSI) Grant Number UL1TR001881. Funding Information: Medical writing support was provided by Michael Sheldon, PhD, and editorial support was provided by George Chappell, MSc, both of Scion (London, UK), supported by Bayer according to Good Publication Practice guidelines. Bayer was involved in fact-checking information provided in the manuscript. However, ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors. Publisher Copyright: {\textcopyright} 2022 Ascend Media. All rights reserved.",
year = "2022",
doi = "10.37765/AJMC.2022.88845",
language = "English (US)",
volume = "28",
pages = "S26--S32",
journal = "American Journal of Managed Care",
issn = "1088-0224",
publisher = "Ascend Media",
}