New Drug Targets Specific Gene Fusions in Rare Pediatric Cancers


Pediatric patients treated with larotrectinib in a clinical trial demonstrated a 93% response rate.

Although most cancer drugs are targeted to specific organs or locations in the body, a first-of-its-kind drug targets a specific fused gene found in many types of cancer, according to a study published in Lancet Oncology.1

The drug was found to be effective in 93% of pediatric patients tested, according to researchers at UT Southwestern’s Simmons Cancer Center.

The targeted fusions, known as TRK fusions, occur when part of the TRK gene becomes attached to another gene—switching on the TRK gene when it’s not supposed to be and causing the cells to grow uncontrollably. The new drug, called larotrectinib, targets these fusions specifically.

TRK fusions only occur in a small percentage of common adult cancers, but can frequently occur in some rare pediatric cancers, such as infantile fibrosarcoma, cellular congenital mesoblastic nephroma, and papillary thyroid cancer. In a clinical study of the drug, patients with TRK fusion-positive solid tumors treated with larotrectinib had their tumor shrink.

In the study, the researchers aimed to assess the safety of larotrectinib in pediatric patients. The trial enrolled infants, children, and adolescents aged 1 month to 21 years with locally-advanced or metastatic solid tumors, or CNS tumors that had relapsed, progressed, or were non-responsive to available therapies regardless of TRK fusion status. Larotrectinib was administered orally twice daily, on a continuous 28-day schedule, in increasing doses adjusted for age and body weight. The primary endpoint of the phase 1 dose escalation component was the drug’s safety, including dose-limiting toxicity.

Of the enrolled patients with TRK fusion-positive cancers, 47% had infantile fibrosarcoma, 41% had other soft tissue sarcomas, and 12% had papillary thyroid cancer. According to the results, larotrectinib was well-tolerated in the patients and showed encouraging antitumor activity.

In a trial including adult patients, which was published in the New England Journal of Medicine, larotrectinib demonstrated a 75% response rate.

“What’s unique about the drug is it is very selective; it only blocks TRK receptors,” Dr Ted Laetsch, lead author, assistant professor of Pediatrics and with the Harold C Simmons Comprehensive Cancer Center, said in a press release.2

The drug’s selectivity means that it does not cause severe adverse effects associated with many traditional cancer treatments, the researchers noted. According to the study, the most common adverse effects of all grades were increased alanine and aspartate aminotransferase, decreased neutrophil count, and vomiting. None of the patients quit the study due to a drug-induced adverse effect.

Additionally, the drug’s response was long-lasting in most patients, which is important because resistance to some targeted drugs can develop quickly. According to the researchers, the next step in research is a clinical trial involving a similar drug for those patients who developed resistance.


1. Laetsch TW, DuBois SG, Mascarenhas L, et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. The Lancet Oncology. Published March 29, 2018.

2. Pediatric cancer drug shows 93 percent response rate [news release]. Dallas. UT Southwestern’s website. Accessed April 2, 2018.

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