In a Children’s Oncology Group study (ADVL1823) reported in Journal of Clinical Oncology, Laetsch et al found that larotrectinib was highly active in patients with newly diagnosed infantile fibrosarcoma and other pediatric NTRK fusion–positive solid tumors.
Study Details
The U.S. multicenter trial enrolled 33 patients between October 2019 and July 2022; of these 18 had infantile fibrosarcoma and 15 had other pediatric NTRK fusion–positive solid tumors. Patients received larotrectinib at 100 mg/m2/dose twice-daily with a maximum of 100 mg/dose twice-daily continuously in 28-day cycles; the drug was given for a predefined duration, ranging from 6 to 26 cycles depending on response to therapy and surgical resectability. The primary endpoint was objective response rate within 6 cycles in patients with infantile fibrosarcoma.
Key Findings
Objective responses within six cycles were observed in 17 of 18 children with infantile fibrosarcoma (94.4%, confidence interval [CI] = 72.7%–98.6%). Objective responses within six cycles were observed in 9 of 15 children with other solid tumors (60.0%, 95% CI = 32.3%–83.7%).
Among all 33 patients, 2 patients (6.1%, 95% CI = 0.7%–22.2%) developed progressive disease during treatment. Event-free survival at 2 years was 82.2% (95% CI = 54.3%–93.9%) in the group of patients with infantile fibrosarcoma and 80% (95% CI = 50.0%–93.1%) in the group with other solid tumors. Overall survival at 2 years was 93.8% (95% CI = 63.2%–99.1%) and 93.3% (95% CI = 61.3%–99.0%), respectively.
Patients undergoing surgical resection exhibited prolonged event-free survival, with disease progression occurring in 1 of 16.
Treatment-related grade ≥ 3 adverse events occurred in 11 patients (33.3%); the only event occurring in more than one patient was neutropenia (n = 6, 18.2%). Dose-limiting adverse events, requiring dose interruption or reduction, occurred in four patients, consisting of neutropenia in two, aspartate transaminase elevation in one, and weight loss in one. No patients discontinued treatment due to adverse events.
The investigators concluded: “Larotrectinib is highly active in patients with newly diagnosed NTRK fusion–positive solid tumors. Larotrectinib should be a front-line option for patients with [infantile fibrosarcoma] and other NTRK fusion–positive solid tumors. Local control with surgical resection remains important in the treatment of patients with [infantile fibrosarcoma].”
Theodore W. Laetsch, MD, of Children’s Hospital of Philadelphia, University of Pennsylvania, is the corresponding author for the Journal of Clinical Oncology article.
Disclosures: The study was supported by grants from the National Cancer Institute, St Baldrick’s Foundation, Alex’s Lemonade Stand Foundation, and Bayer. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
