Larotrectinib Demonstrates Efficacy, Safety for Patients With TRK Fusion-Positive Gastrointestinal Cancers

According to results from a retrospective analysis, larotrectinib, a first-in-class, selective tropomyosin receptor kinase (TRK) inhibitor, demonstrated efficacy and safety among patients with TRK fusion gastrointestinal cancers, including colorectal cancer (CRC). 

Based on results from previous phase 1/2 trials, larotrectinib “has received tumour-agnostic approval for the treatment of adult and paediatric patients with TRK fusion solid tumours,” stated Changsong Qi, MD, PhD, Peking University Cancer Hospital and Institute, Beijing, China, and coauthors. Here, researchers report “the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer from the NAVIGATE clinical trial.” 

In this analysis, researchers included patients who were enrolled in the phase 2 NAVIGATE trial. At the time of analysis, there were 44 patients with locally advanced or metastatic TRK fusion gastrointestinal cancers who had initiated on larotrectinib (CRC, n = 26; pancreatic cancer, n = 7; cholangiocarcinoma, n = 4; gastric. n = 3; appendiceal, duodenal, oesophageal, and hepatic cancers, n = 1 of each). Patients received 100 mg of twice daily larotrectinib until disease progression or unacceptable toxicity. The primary end point of this analysis was overall response rate (ORR) in both the intention-to-treat population and in patients with CRC. Key secondary end points included duration of response, progression-free survival (PFS), overall survival (OS), and safety. 

At analysis, the ORR was 28% in the intention-to-treat population and 44% among patients with CRC. The median duration of response was 27 months. Median PFS was 6 months in the intention-to-treat population and 7 months among patients with CRC. There was a median OS of 13 months and 29 months, respectively. Grade 3/4 treatment-related adverse events were reported by 16% of patients. No treatment-related deaths occurred. 

“Larotrectinib demonstrated long durability, extended survival, and manageable safety in patients with TRK fusion GI cancer,” concluded Dr Qi et al. “This supports the wider adoption of next-generation sequencing testing for NTRK gene fusions in patients with GI cancer.”

Source: 

Qi C, Shen L, Andre T, et al. Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer. Eur J Oncol. Published online: March 4, 2025. doi: 10.1016/j.ejca.2025.115338