Research in context
Evidence before this study
We searched PubMed and major congress abstracts (including those from meetings of the American Society of Clinical Oncology and the American Association for Cancer Research) using the terms “TRK or NTRK”, “fusion or rearrangement”, “cancer” and “treatment”. We did not restrict our search by publication date or language. The results of this search showed that TRK inhibition with the first-generation TRK inhibitors larotrectinib or entrectinib was active in TRK fusion-positive cancers of various histologies. Both drugs had been approved by multiple regulatory agencies for the treatment of TRK fusion-positive cancers in both adult and paediatric populations. The next-generation TRK inhibitors selitrectinib or repotrectinib showed preliminary activity in small series that included patients with resistance to first-generation TRK inhibitors.
Added value of this study
In the initial analysis of the first 55 consecutively enrolled adult and paediatric patients with TRK fusion cancer who were treated with larotrectinib, the durability of benefit and long-term safety had not been fully characterised. This expanded efficacy analysis includes data on the durability of disease control in a combined efficacy population almost three times larger than previously reported. Additionally, our expanded safety analysis in 260 patients confirms the favourable tolerability profile of larotrectinib, including in patients with longer treatment durations.
Implications of all the available evidence
TRK fusions define a unique molecular subgroup of advanced solid tumours for which the activity of larotrectinib is highly durable. Long-term safety is favourable. Our findings underscore the need to test for TRK fusions in the clinic with assays that are best poised to identify these alterations.