Precision Drug Effective in Children, Adults with Different Cancers

Experimental drug elicits response in diverse population of patients with cancer.

With the move towards individualized medicine, cancer treatment decisions are now largely based on myriad factors, including patient genes and age. The findings from a study published by the New England Journal of Medicine suggests that a large number of adult and pediatric patients with different cancers may respond to a novel drug that targets a genetic mutation.

During the phase 1/2 trial, 75% of participants with cancers that affect various parts of the body responded to treatment with larotrectinib. The drug, which targets the genetic traits of a tumor instead of its origin, shows promise as a more effective therapy, according to the authors.

Included in the trial were 55 patients with 17 unique tumor types who ranged in age from 4 months to 76 years. All patients had a genetic defect called TRK fusions, which are known to increase cancer growth.

Patients were treated with oral larotrectinib, which selectively inhibits the process of TRK fusion proteins.

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The researchers found that 75% of patients responded to therapy, with 86% of all patients still on therapy or having undergone surgery. There were no discontinuations related to adverse events, according to the study.

“Ongoing treatment with larotrectinib continues to demonstrate striking and durable efficacy coupled with minimal side effects, across a diverse patient population,” said senior author David Hyman, MD. “The efficacy of larotrectinib warrants screening for TRK fusions alongside other actionable targets in patients of all ages with advanced solid tumors.”

Several of the pediatric patients were diagnosed with infantile fibrosarcoma, a type of cancer that features a TRK fusion. This type of cancer is hard to treat because it typically responds poorly to chemotherapy and radiation therapy can have serious ill effects on young patients, according to the authors.

“In some cases, this cancer can be treated surgically—often requiring amputation or another disfiguring surgical procedure,” said Leo Mascarenhas, MD, MS, who helped design the clinical trial. “After treating our patient with infantile fibrosarcoma with larotrectinib, the cancer shrunk sufficiently, and we were able to surgically remove the tumor while preserving the patient’s leg.”

The authors noted that the drug development program for larotrectinib is innovative, in that clinical trials in children generally occur after the product is approved for adults, while larotrectinib was tested concurrently in these populations.

For very young pediatric patients, a liquid formulation was developed to administer clinically appropriate doses. The assessment of larotrectinib in very young patients may help expedite approval in all populations, according to the authors.

“This is truly a magic bullet for our patients with TRK-positive cancer,” Dr Mascarenhas said.

Larotrectinib previously received FDA breakthrough therapy designation for the treatment of unresctable or metastatic solid tumors with TRK fusion proteins in both adults and pediatric patients, according to a Loxo Oncology press release.