Abstract
Background: Larotrectinib, a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor, has demonstrated efficacy in adult and pediatric patients with various solid tumors harboring NTRK gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas. Methods: Patients (≥18 years old) with sarcomas harboring NTRK gene fusions were identified from three clinical trials. Patients received larotrectinib 100 mg orally twice daily. Response was investigator-assessed per RECIST v1.1. Data cutoff was July 20, 2021. Results: At the data cutoff, 36 adult patients with TRK fusion sarcomas had initiated larotrectinib therapy: two (6%) patients had bone sarcomas, four (11%) had gastrointestinal stromal tumors, and 30 (83%) had soft tissue sarcomas. All patients were evaluable for response and demonstrated an objective response rate of 58% (95% confidence interval, 41–74). Patients responded well to larotrectinib regardless of number of prior lines of therapy. Adverse events (AEs) were mostly grade 1/2. Grade 3 treatment-emergent AEs (TEAEs) occurred in 15 (42%) patients. There were no grade 4 TEAEs. Two grade 5 TEAEs were reported, neither of which were considered related to larotrectinib. Four (11%) patients permanently discontinued treatment due to TEAEs. Conclusions: Larotrectinib demonstrated robust and durable responses, extended survival benefit, and a favorable safety profile in adult patients with TRK fusion sarcomas with longer follow-up. These results continue to demonstrate that testing for NTRK gene fusions should be incorporated into the clinical management of adult patients with various types of sarcomas. Plain Language Summary: Tropomyosin receptor kinase (TRK) fusion proteins result from translocations involving the NTRK gene and cause cancer in a range of tumor types. Larotrectinib is an agent that specifically targets TRK fusion proteins and is approved for the treatment of patients with TRK fusion cancer. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. Over half of patients had a durable response to larotrectinib, with no unexpected side effects. These results show that larotrectinib is safe and effective in adult patients with TRK fusion sarcomas.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Cancer |
| Vol/bind | 129 |
| Udgave nummer | 23 |
| Sider (fra-til) | 3772-3782 |
| Antal sider | 11 |
| ISSN | 0008-543X |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
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 Cindy Cheung, MBBS (MD) and Luke Springall, PhD, editorial support was provided by George Chappell, MSc, and Melissa Ward, BA, all of Scion, London UK, supported by Bayer according to Good Publication Practice guidelines (Link). The sponsor was involved in the study design and 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. These studies were funded by Bayer HealthCare and Loxo Oncology, Inc, a wholly owned subsidiary of Eli Lilly and Company. Alexander Drilon was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.
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 Cindy Cheung, MBBS (MD) and Luke Springall, PhD, editorial support was provided by George Chappell, MSc, and Melissa Ward, BA, all of Scion, London UK, supported by Bayer according to Good Publication Practice guidelines (Link). The sponsor was involved in the study design and 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. These studies were funded by Bayer HealthCare and Loxo Oncology, Inc, a wholly owned subsidiary of Eli Lilly and Company. Alexander Drilon was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.
Publisher Copyright:
© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.