Neoadjuvant TRK inhibitors versus chemotherapy in advanced NTRK fusion-positive sarcomas: a real-world evidence analysis

作者：Fuyi Zhu, Haiyan Cheng, Yali Han, Yang Shen, Zhiyun Zhu, Qinghua Ren, Yan Su, Zhenni Wang, Hong Qin, Wei Yang, Shan Wang, Yijin Gao, Huanmin Wang · 发表于：The Oncologist · 年份：2025 · DOI：10.1093/oncolo/oyaf401 · 被引用次数：1 · 研究领域：Lung Cancer Treatments and Mutations、Sarcoma Diagnosis and Treatment、Melanoma and MAPK Pathways

IMPORTANCE: Despite the proven efficacy of tropomyosin receptor kinase (TRK) inhibitors in advanced neurotrophic tyrosine receptor kinase (NTRK) fusion-positive sarcomas, chemotherapy remains the default first-line therapy in many developing countries. OBJECTIVE: This real-world study directly compares outcomes of TRK inhibitors with chemotherapy. DESIGN: This was a multicenter, retrospective cohort study. SETTING: 50 children with advanced NTRK fusion-positive sarcomas were analyzed from three study centers (2018-2024). INTERVENTION: Patients were assigned into two groups according to their choice of treatment,including chemotherapy or TRK inhibitors.. MAIN OUTCOMES AND MEASURES: Endpoints included treatment failure rate, objective response rate (ORR), mutilating surgery, time to treatment failure, and event-free survival (EFS). Subgroup analyses were conducted for infantile fibrosarcoma (IFS) and NTRK-rearranged spindle cell tumors. RESULTS: The efficacy of TRK inhibitors (n = 37) was markedly superior compared to chemotherapy (n = 13). Treatment failure was almost eliminated (2.7% vs. 61.5%, P < 0.001), and ORR was significantly higher (91.9% vs. 53.8%, P = 0.006). Subgroup analysis revealed that TRK inhibitors prevented mutilating surgery in IFS (0.0% vs. 42.9%, P < 0.001) and improved the ORR in NTRK-rearranged spindle-cell tumors (95.0% vs. 0.0%, P < 0.001) in which chemotherapy was ineffective. TRK inhibition also induced faster tumor shrinkage, smaller preoperative bu...