Researchers from the Children's Hospital of Philadelphia (CHOP) and the Children's Oncology Group (COG) have found that larotrectinib, an oral drug, is highly effective in pediatric patients with newly diagnosed infantile fibrosarcoma (IFS) or other solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation. The study, published in the Journal of Clinical Oncology, suggests that larotrectinib could replace chemotherapy as a first-line therapy for certain cancers.
The study is the first COG trial to test precision medicine in a front-line setting across different types of solid tumors based on a genetic biomarker rather than histology. This approach is poised to redefine the treatment of newly diagnosed fibrosarcoma and other solid tumors with the NTRK gene fusion, potentially reducing or eliminating the need for chemotherapy.
Study Details and Findings
The study analyzed 33 patients between October 2019 and July 2022, including 18 with IFS and 15 with other solid tumors. The patients, with a median age of 8, received larotrectinib twice daily in 28-day cycles for a predefined duration of treatment, ranging from 6 to 26 cycles depending on response to therapy and whether the tumor could be safely removed with surgery. The primary endpoint was the objective response rate (ORR) within six cycles in patients with IFS.
The ORR 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. The two-year event-free survival (EFS) and overall survival (OS) among these groups were 82.2% and 93.8% for IFS and 80% and 93.3% for other solid tumors. Patients undergoing surgical resection of their tumor had prolonged EFS.
Implications for Treatment
"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 Theodore W. Laetsch, MD, lead study author and a pediatric oncologist 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."
About Larotrectinib
Larotrectinib was approved in 2018 by the U.S. Food and Drug Administration (FDA) 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. Unlike traditional treatments directed at specific cancers based on their location in the body, larotrectinib targets the NTRK fusion present in the tumor, making it effective across various cancer types that share this mutation.
