Precision drug could treat different cancers with rare gene fault  

Cancer Research UK

A new targeted drug could be used to treat a small number of advanced cancers no matter where they grow in the body.  

Three quarters of patients with advanced cancers that share a rare gene fault responded to the experimental drug, called larotrectinib (LOXO-101), according to results pooled from small clinical trials. 

The innovative approach, published in the New England Journal of Medicine, involved 55 patients with 17 different types of cancer. Everyone in the trial had a gene fault called a TRK fusion, which occurs in less than 1 in 100 tumours and can fuel growing cancer cells.  

Larotrectinib was developed to specifically target cancer cells that carry this gene fault. Developing and testing the drug in this way is different to many trials, which focus on a specific type of cancer.  

What did the trial show?  

The trial included patients with soft tissue sarcomas, thyroid and bowel cancer, and 1 in 5 patients in the trial had salivary gland cancer. Patients ranged from 4 months to 76 years old.  

Over half the cancers hadn't worsened one year after treatment.  

When the researchers reviewed if the patients’ cancers had responded: 

  • 7 patients had seen their cancer disappear 
  • 34 had seen their cancer shrink to some degree 
  • 7 had seen their cancer remain stable and not grow 
  • 5 had seen their cancer get worse 
  • 2 withdrew from the trial because their condition deteriorated 

The main side effects that patients experienced were early signs of liver damage, dizziness and vomiting. Most reactions were mild, according to the researchers.  

Stepping up to the challenge 

Many of the gene faults found inside cancer cells, such as TRK fusions, are rare.  

“This makes it very challenging to design clinical trials for patients with a particular type of cancer that carries these mutations because the numbers are small," said Professor Charles Swanton, Cancer Research UK's chief clinician.   

"In situations like these, early stage clinical trials involving patients with multiple types of cancer are the only option to test new drugs."  

New options 

Several children on the trial had a type of cancer called infantile fibrosarcoma. Dr Leo Mascarenhas, from Children's Hospital Los Angeles and who helped design the study, said this cancer can be treated with surgery, but this can be severe and disfiguring. 

“After treating our patient with infantile fibrosarcoma with larotrectinib, the cancer shrunk sufficiently and we were able to surgically remove the tumour while preserving the patient's leg," he said. 

Surgery also became an option for other patients whose cancers shrank following treatment with the drug.  


Drilon, A. et al. (2018). Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children. New England Journal of Medicine. DOI: 10.1056/NEJMoa1714448