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

Background Tropomyosin receptor kinase (TRK) fusions arise from rearrangements of the neurotrophic tyrosine receptor kinase (NTRK) 1, 2, or 3 genes and an unrelated gene, creating constitutively active oncogenic drivers that have been detected in a range of adult and pediatric malignancies, but are generally rare in patients with gastrointestinal (GI) cancer. Larotrectinib is a selective TRK inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. Here, we report efficacy and safety data for patients with TRK fusion GI tumors.

Methods Patients with a TRK fusion GI cancer treated with larotrectinib in a phase II clinical trial, NAVIGATE, were included in this analysis. Larotrectinib was administered at 100 mg twice daily, until disease progression, unacceptable toxicity, death, or withdrawal. Response was assessed by the investigator using RECIST v1.1.

Results As of February 19, 2019, 14 patients with TRK fusion GI cancer (median age 68 y, range 32-84 y) were enrolled. GI tumor types were colon (8), cholangiocarcinoma (2), pancreas (2), appendix (1), and hepatic (1). Fusions involved NTRK1 (n = 12) and NTRK3 (n = 2). Nine patients had ≥2 prior lines of therapy. The best response on last prior therapy was 1 partial response (PR). Overall best responses on larotrectinib were: colon cancer, 4 patients had a PR and 4 had stable disease (SD); pancreatic cancer, 1 patient had a PR and 1 had SD; cholangiocarcinoma, 1 patient had a PR and 1 had progressive disease; appendix cancer, 1 patient had SD; response in 1 patient with hepatic cancer was not determined. Median time to response was 1.8 months (range 1.7-2.1). With 5 patients ongoing and censored, the median progression free survival was 5.3 months (95% CI 2.2-9.0). Median overall survival was 33.4 months (95% CI 2.8-36.5). Larotrectinib was well tolerated, with most AE being grade 1 or 2.

Conclusions Although the sample size is limited, there is evidence of clinical activity with larotrectinib in TRK fusion GI cancer, with a manageable safety profile. TRK fusion GI cancer may represent an under-diagnosed subset of patients with viable treatment options.

© 2020 ASCO, Inc. Reused with permission. This abstract was accepted and previously presented at the 2020 ASCO GI Meeting.

Publikationsverlauf

Artikel online veröffentlicht:
08. September 2020