Innovative Precision Medicine Achieves Promising Outcomes for Infantile Fibrosarcoma and Additional Solid Tumors

Recent research conducted by the Children's Hospital of Philadelphia (CHOP) and the Children's Oncology Group (COG) has demonstrated that larotrectinib, an oral medication designed to inhibit cancer cell proliferation, shows significant efficacy in young patients newly diagnosed with infantile fibrosarcoma (IFS) and other solid tumors characterized by a neurotrophic receptor tyrosine kinase (NTRK) gene fusion, provided there is no known acquired resistance mutation.

This groundbreaking study, which was published in the Journal of Clinical Oncology, represents the first COG trial aimed at evaluating precision medicine in a front-line context across various solid tumor types based on genetic biomarkers rather than traditional histological classifications. The findings may revolutionize treatment protocols for newly diagnosed fibrosarcoma and other solid tumors with NTRK gene fusions, potentially minimizing or even eliminating the need for chemotherapy in these pediatric patients.

According to the lead researcher at CHOP, the shift towards precision medicine is reshaping pediatric oncology by offering customized treatment options that promise improved outcomes and brighter prospects for young patients and their families.

Infantile fibrosarcoma is classified as a rare soft-tissue sarcoma that typically manifests as a localized tumor. Although surgical intervention often results in a cure, infants frequently present with rapidly growing tumors that are inoperable, necessitating chemotherapy, which can pose significant risks to their developing organs and tissues.

Larotrectinib received approval from the U.S. Food and Drug Administration (FDA) in 2018 for use in both pediatric and adult patients with solid tumors exhibiting an NTRK gene fusion, particularly those that are metastatic or where surgery would entail considerable risks, as well as for patients who have exhausted other treatment options or whose cancer has progressed after therapy.

Unlike conventional treatments that target specific cancers based on their anatomical location, larotrectinib specifically addresses the NTRK fusion present in the tumor, making it applicable across various cancer types that share this genetic alteration. Previous research has explored the use of precision medicines for neuroblastoma and Ewing's sarcoma, but this study is unique in enrolling patients with any cancer type based on a specific genetic mutation.

The investigation encompassed 33 pediatric patients from October 2019 to July 2022, including 18 with IFS and 15 with other solid tumors. The median age of participants was eight years, and they received larotrectinib twice daily in 28-day cycles for a predetermined duration, which varied from six to 26 cycles based on individual responses to the therapy and the possibility of surgical removal of the tumor.

The primary endpoint of the study was the objective response rate (ORR) within the first six cycles for patients diagnosed with IFS, defined as the percentage of subjects whose tumors either shrank or completely disappeared as determined by medical assessments. Secondary objectives included event-free survival (EFS) and overall survival (OS).

The ORR within the first six cycles was reported at 94% for children with IFS and 60% for those with other solid tumors. Unfortunately, two patients--one with IFS and another with a different type of solid tumor--did experience disease progression while undergoing treatment and subsequently succumbed to their illness. Two-year EFS and OS rates were recorded at 82.2% and 93.8% for IFS patients, and 80% and 93.3% for those with other solid tumors, respectively. Patients who underwent surgical resection of their tumors exhibited extended EFS.

This trial establishes larotrectinib as the primary treatment option for patients newly diagnosed with fibrosarcoma and other solid tumors featuring an NTRK gene fusion. The overarching aim of this research is to present the safest and most effective treatment strategies for pediatric patients, focusing on minimizing both immediate and long-term complications associated with chemotherapy.

Further details on this study can be found in the Journal of Clinical Oncology.