The FDA granted accelerated approval to Loxo Oncology and Bayer's larotrectinib for patients with solid tumours that have neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Larotrectinib is the first drug to be developed entirely for a tissue-agnostic cancer indication that doesn't depend on where the cancer originated.

Last year the FDA granted a supplementary approval to Merck & Co's PD1 blocker pembrolizumab for microsatellite instability-high (MSI-H) tumours, but this immunotherapeutic antibody is also used widely on a tissue-dependent basis.

The FDA's approval of larotrectinib was based on data from three open-label, single-arm trials of the drug. The first 55 patients with NTRK fusion-positive cancers enrolled into the trial had an overall response rate of 75%. The median duration of the response had not been reached at the time of data lock, but 73% of patients reached at least 6 months, and 39% of patients reached at least 12 months.

NTRK fusions, which result in persistent oncogenic signalling, are thought to be present in <1% of all solid tumours. Analysts have forecast annual sales of US$500 million to $1 billion for the drug, but have noted that Loxo and Bayer may have difficulties identifying potentially responsive patients and overcoming tissue-based thinking among oncologists.

Some oncologists suspect that opportunities for tissue-agnostic drugs may be few and far between, but a number of other such candidates are in development (Nature Reviews Drug Discovery 17, 227–229; 2018). Ignyta and Roche's entrectinib is in phase II development for NTRK fusion-positive solid cancers, as a potential competitor to larotrectinib. Loxo as well as Ignyta and their partner Roche are also working on earlier-stage clinical candidates for RET-mutant solid tumours. And Plexxikon is exploring tissue-agnostic potential in KIT-mutant and BRAF-mutant solid tumours.