Two clinical studies have provided evidence suggesting that an experimental precision-medicine drug called larotrectinib can fight soft-tissue tumors regardless of the patient’s age or the type of tumor.
Seattle Children’s Hospital participated in both studies.
The first study, published last month in the New England Journal of Medicine, found that 75 percent of the patients who had a genetic mutation in their tumors known as tropomyosin receptor kinase fusion, or TRK fusion, responded to treatment. After a year of treatment, 71 percent showed no signs of disease progression.
The Phase 1/2 clinical trial collected data from a pool of 55 patients, ranging in age from 4 months to 76 years, with 17 different types of TRK fusion-positive tumors. Six of the participants in the study were pediatric patients at Seattle Children’s Hospital.
“Most drugs aren’t tested in children until they are much further along in the approval process, so including children this early in the process was very unusual,” Seattle Children’s cancer researcher Doug Hawkins, a co-author of the study, said in a report from the hospital.
Hawkins is also the senior author of a study published this week in The Lancet Oncology, focusing specifically on larotrectinib’s effect on children and adolescents ranging in age from 1 month to 21 years. The trial involved 22 experimental subjects — 15 with TRK fusion-positive tumors, and seven whose tumors did not have the TRK-fusion mutation. (Two other patients who were enrolled in the study had no measurable signs of disease.)
Larotrectinib had no effect on the non-TRK tumors, but 14 of the 15 patients with TRK fusion-positive tumors responded to treatment. The other patient had an initial partial response that was subsequently assessed as stable disease.
“Our results indicate that larotrectinib is tolerable, with responses observed in a high proportion of infants, children and adolescents with advanced TRK fusion-positive solid tumors,” the researchers reported.
They said larotrectinib could offer a new treatment option for some cancer patients who might otherwise face disfiguring surgery.
Lead study author Ted Laetsch, a cancer researcher at UT Southwestern Medical Center in Dallas, said the drug showed promise for treating any tumor with the TRK-fusion genetic mutation, which causes cells to grow uncontrollably.
“What’s unique about the drug is, it is very selective,” Laetsch said in a news release. “It only blocks TRK receptors.”
Larotrectinib, which is being developed for clinical use by Connecticut-based Loxo Oncology, won a breakthrough therapy designation for the experimental drug from the Food and Drug Administration in 2016. Further trials will be required for full FDA approval.
Lead author of the New England Journal of Medicine study, “Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children,” is Alexander Drilon of Memorial Sloan Kettering Cancer Center. In addition to Hawkins, Seattle co-authors include Christina Baik (Seattle Cancer Care Alliance) and Erin Rudzinski (Seattle Children’s Hospital).
In addition to Hawkins, Seattle co-authors of the study in The Lancet Oncology, “Larotrectinib for Paediatric Solid Tumours Harbouring NTRK Gene Fusions: Phase 1 Results from a Multicentre, Open-label, Phase 1/2 Study,” include Catherine Albert, Jessica Davis and Erin Rudzinski of Seattle Children’s Hospital.