Stanford Cancer Center, Stanford University, Palo Alto, California, USA.
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
Cancer. 2023 Dec 1;129(23):3772-3782. doi: 10.1002/cncr.35036. Epub 2023 Sep 28.
Larotrectinib, a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor, has demonstrated efficacy in adult and pediatric patients with various solid tumors harboring NTRK gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas.
Patients (≥18 years old) with sarcomas harboring NTRK gene fusions were identified from three clinical trials. Patients received larotrectinib 100 mg orally twice daily. Response was investigator-assessed per RECIST v1.1. Data cutoff was July 20, 2021.
At the data cutoff, 36 adult patients with TRK fusion sarcomas had initiated larotrectinib therapy: two (6%) patients had bone sarcomas, four (11%) had gastrointestinal stromal tumors, and 30 (83%) had soft tissue sarcomas. All patients were evaluable for response and demonstrated an objective response rate of 58% (95% confidence interval, 41-74). Patients responded well to larotrectinib regardless of number of prior lines of therapy. Adverse events (AEs) were mostly grade 1/2. Grade 3 treatment-emergent AEs (TEAEs) occurred in 15 (42%) patients. There were no grade 4 TEAEs. Two grade 5 TEAEs were reported, neither of which were considered related to larotrectinib. Four (11%) patients permanently discontinued treatment due to TEAEs.
Larotrectinib demonstrated robust and durable responses, extended survival benefit, and a favorable safety profile in adult patients with TRK fusion sarcomas with longer follow-up. These results continue to demonstrate that testing for NTRK gene fusions should be incorporated into the clinical management of adult patients with various types of sarcomas.
Tropomyosin receptor kinase (TRK) fusion proteins result from translocations involving the NTRK gene and cause cancer in a range of tumor types. Larotrectinib is an agent that specifically targets TRK fusion proteins and is approved for the treatment of patients with TRK fusion cancer. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. Over half of patients had a durable response to larotrectinib, with no unexpected side effects. These results show that larotrectinib is safe and effective in adult patients with TRK fusion sarcomas.
拉罗替尼是一种首创的、高度选择性的原肌球蛋白受体激酶（TRK）抑制剂，已在携带 NTRK 基因融合的各种实体瘤的成人和儿科患者中显示出疗效。本亚组分析重点关注拉罗替尼在扩展的成人 TRK 融合肉瘤患者队列中的疗效和安全性。
从三项临床试验中确定了携带 NTRK 基因融合的肉瘤患者（≥18 岁）。患者接受拉罗替尼 100mg 口服，每日两次。根据 RECIST v1.1 评估应答。数据截止日期为 2021 年 7 月 20 日。
数据截止时，36 名患有 TRK 融合肉瘤的成年患者开始接受拉罗替尼治疗：两名（6%）患者患有骨肉瘤，四名（11%）患有胃肠道间质瘤，30 名（83%）患有软组织肉瘤。所有患者均可评估反应，客观缓解率为 58%（95%置信区间，41-74）。无论先前治疗线数如何，患者对拉罗替尼的反应均良好。不良事件（AE）主要为 1/2 级。15 名（42%）患者发生 3 级治疗后出现的 AE（TEAE）。无 4 级 TEAE。报告了 2 例 5 级 TEAE，均与拉罗替尼无关。4 名（11%）患者因 TEAE 永久停药。
在接受更长时间随访的 TRK 融合肉瘤成年患者中，拉罗替尼显示出强大且持久的反应、延长的生存获益和良好的安全性。这些结果继续表明，应将 NTRK 基因融合检测纳入各种类型肉瘤成人患者的临床管理中。
