There’s new evidence that Larotrectinib (Vitrakvi), by Loxo Oncology and Bayer, is highly effective in children with newly diagnosed infantile fibrosarcoma (IFS) or other solid tumors. This is according to a study from researchers at the Children’s Hospital of Philadelphia (CHOP) and the Children’s Oncology Group (COG). The drug targets tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation. Larotrectinib was FDA approved for solid tumors in 2018.
The study was published in the Journal of Clinical Oncology. The lead author is Theodore W. Laetsch, MD, Children’s Hospital of Philadelphia.
The researchers report that this is the first COG trial to test precision medicine in a front-line setting across all different types of solid tumors based on a genetic biomarker rather than histology. The study, they say. “is poised to redefine the approach to treatment for newly diagnosed fibrosarcoma and other solid tumors with the NTRK gene fusion, potentially reducing or eliminating the need for these patients to receive chemotherapy.”
“Precision medicine is transforming pediatric cancer care, offering tailored treatments that bring new hope for better outcomes and a brighter future for children and their families,” said Laetsch, a pediatric oncologist at CHOP, who leads the hospital’s Developmental Therapeutics Program and Very Rare Malignant Tumors Program, as well as holding national leadership roles in each of these areas within COG.
IFS, a rare soft-tissue sarcoma, typically presents as a localized tumor. Although surgery often cures IFS, infants frequently present with fast-growing tumors that can’t be removed with surgery and require chemotherapy, which can pose serious harm to a young child’s developing organs and tissues.
In 2018, Larotrectinib was FDA approved for pediatric and adult patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, that are either metastatic or where surgical resection is likely to have severe side effects, and who have no satisfactory alternative treatments or whose cancer has progressed following treatment.
Larotrectinib could be effective across various cancer types that share the NTRK fusion mutation. Researchers have previously conducted front-line research of precision medicines for neuroblastoma and Ewings sarcoma, however, this, the team says, is the first study to enroll patients with any cancer based on a specific genetic mutation.
In this study, researchers analyzed 33 patients between October 2019 and July 2022: 18 with IFS and 15 with other solid tumors. The patients, whose median age was eight, received larotrectinib twice daily in 28-day cycles for a predefined duration of treatment, ranging from six to twenty-six cycles depending on response to therapy and whether the tumor could be safely removed with surgery.
The objective response rate within six cycles was 94% among children with IFS and 60% among children with other solid tumors. Two patients, one with IFS and one with a different solid tumor, experienced disease progression while on the therapy and eventually died of their disease.
“This trial cements larotrectinib as the frontline therapy for patients with newly diagnosed fibrosarcoma and other solid tumors that also possess an NTRK gene fusion,” said Laetsch, who is also a member of the cellular therapy/chimeric antigen receptor (CAR) T-cell team at CHOP. “Our goal is always to present the safest and most effective treatment approach for our patients, which includes sparing them from the short and long-term complications of chemotherapy.”
