Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer

Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer. Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1. As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients with CRC, 16 (62 %) had known microsatellite instability-high (MSI-H) status. For the 43 IRC-eligible patients, overall response rate was 28 % (95 % confidence interval [CI] 15-44) for all patients and 44 % (95 % CI 24-65) for those with CRC. In patients overall and in those with CRC, median duration of response was 27 months (95 % CI 6-not estimable [NE]) and 27 months (95 % CI 6-NE), median progression-free survival was 6 months (95 % CI 5-9) and 7 months (95 % CI 6-NE), and median overall survival was 13 months (95 % CI 7-29) and 29 months (95 % CI 7-NE), respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in seven (16 %) patients. There were no deaths due to TRAEs. Larotrectinib demonstrated long durability, extended survival and manageable safety in patients with TRK fusion GI cancer, including those with MSI-H CRC. This supports the wider adoption of next-generation sequencing testing for NTRK gene fusions in patients with GI cancer.