1955P Survival benefits of larotrectinib in an integrated dataset of patients with TRK fusion cancer

Larotrectinib is a first-in-class, CNS-active, EMA- and FDA-approved selective tropomyosin receptor kinase (TRK) inhibitor. TRK proteins are encoded by the NTRK genes; gene fusions involving NTRK are rare oncogenic drivers seen in a range of paediatric and adult tumour types. Pooled analysis of three clinical trials showed that larotrectinib induced an investigator-assessed overall response rate (ORR) of 79%, median progression-free survival (PFS) of 28.3 months (95% CI 22.1–NE) and median overall survival (OS) of 44.4 months (95% 36.5–NE) in 159 patients (pts) with TRK fusion cancer (Hong et al, Lancet Oncol. 2020). Here we report updated survival data with longer follow-up in an integrated dataset of 175 pts with TRK fusion cancer treated with larotrectinib. Data were pooled from three clinical trials of pts with non-primary CNS TRK fusion cancer treated with larotrectinib. Disease status was assessed by investigators using RECIST v1.1. Primary endpoint was ORR and secondary endpoints included PFS, OS, duration of response (DoR) and safety outcomes. Data cut-off: 15 July 2019. A total of 175 pts were included in the integrated dataset. The median age was 43 y (range 0.1–84.0). The ORR was 78% (95% CI 71–84): 19% complete response, 59% partial response, 13% stable disease and 7% progressive disease. Median DoR was not estimable (NE) at a median follow-up of 13.5 months, with a 12-month DoR rate of 81% (95% CI 73–89). At a median follow-up of 13.8 months, median PFS was 36.8 months (95% CI 25.7–NE), showing extended benefit compared to previous analysis. Although median OS had not been reached with a median follow-up of 15.3 months, the 12-month OS rate was 90% (95% CI 85–95). Larotrectinib-related adverse events (AEs) were mainly Grade 1/2 with no new safety signals identified; two pts discontinued due to larotrectinib-related AEs. These data confirm that treatment with larotrectinib offers extended survival benefit in pts with TRK fusion cancer. Larotrectinib continued to demonstrate a favourable long-term safety profile. Screening pts for NTRK gene fusions should be actively considered.