As reported in the Journal of Clinical Oncology by Mascarenhas et al, follow-up of a cohort of pediatric patients with TRK fusion sarcomas and related mesenchymal tumors treated with larotrectinib showed that discontinuation of treatment—with resumption for progressive disease—was associated with good outcomes.
Study Details
The study included 91 patients (aged < 18 years) receiving larotrectinib in two clinical trials, with infantile fibrosarcoma in 49, other soft-tissue sarcomas or related mesenchymal tumors in 41, and bone sarcoma in 1. In a “wait-and-see” strategy, patients could stop larotrectinib in the event of on-study surgical resection or ongoing nonsurgical complete response, partial response for at least 1 year, or stable disease for at least 2 years. Patients who stopped larotrectinib were followed and could resume treatment for disease progression.
Key Findings
Objective response to initial larotrectinib treatment was observed in 87% of patients (95% confidence interval [CI] = 78%–93%). This included a complete response in 52% and a partial response in 35%; an additional 8% of patients had stable disease.
In the wait-and-see analysis, 47 patients discontinued larotrectinib. The median time from the start of initial larotrectinib treatment to its discontinuation was 14.7 months. After a median follow-up of 41.3 months (95% CI = 31.0–50.0 months), the median time to disease progression in the 47 patients was not reached (range = 0+ to 77.6+ months). A total of 16 patients (34%) exhibited disease progression during the wait-and-see period; all 16 patients resumed larotrectinib, with disease control achieved in 15 (94%), and an objective response observed in 11 (69%), including a complete response in 5 patients. All 47 patients in the wait-and-see group were alive at data cutoff.
The investigators concluded: “Larotrectinib continues to demonstrate durable responses with favorable safety in children with TRK fusion sarcomas. Treatment discontinuation is feasible in select patients with objective response and clinical benefit noted in those who have disease progression after elective treatment discontinuation.”
Leo Mascarenhas, MD, MS, of Cedars-Sinai Medical Center, Los Angeles, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bayer Healthcare and Loxo Oncology, Inc, a wholly owned subsidiary of Eli Lilly and Company. For full disclosures of the study authors, visit ascopubs.org.
