Larotrectinib efficacy and safety in adult patients with tropomyosin receptor kinase fusion sarcomas

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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 <jats:italic>NTRK</jats:italic> gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients (≥18 years old) with sarcomas harboring <jats:italic>NTRK</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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 <jats:italic>NTRK</jats:italic> gene fusions should be incorporated into the clinical management of adult patients with various types of sarcomas.</jats:p></jats:sec><jats:sec><jats:title>Plain Language Summary</jats:title><jats:p> <jats:list list-type="bullet"> <jats:list-item><jats:p>Tropomyosin receptor kinase (TRK) fusion proteins result from translocations involving the <jats:italic>NTRK</jats:italic> gene and cause cancer in a range of tumor types.</jats:p></jats:list-item> <jats:list-item><jats:p>Larotrectinib is an agent that specifically targets TRK fusion proteins and is approved for the treatment of patients with TRK fusion cancer.</jats:p></jats:list-item> <jats:list-item><jats:p>This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins.</jats:p></jats:list-item> <jats:list-item><jats:p>Over half of patients had a durable response to larotrectinib, with no unexpected side effects.</jats:p></jats:list-item> <jats:list-item><jats:p>These results show that larotrectinib is safe and effective in adult patients with TRK fusion sarcomas.</jats:p></jats:list-item> </jats:list> </jats:p></jats:sec>