PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：拉罗列替尼，一流的，高选择性原肌球蛋白受体激酶（TRK）抑制剂，已证明对患有NTRK基因融合的各种实体瘤的成人和儿童患者有效。此亚组分析的重点是拉罗列替尼在扩大的TRK融合肉瘤成年患者队列中的疗效和安全性。
方法：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）。患者每天两次口服larotrectinib100mg。响应是根据RECISTv1.1的研究者评估的。数据截止日期为2021年7月20日。
结果：在数据截止处，36名TRK融合肉瘤的成人患者开始了larotrectinib治疗：两名（6％）患者患有骨肉瘤，四个（11%）有胃肠道间质瘤，30例（83％）有软组织肉瘤。所有患者均可评估反应，客观反应率为58%（95%置信区间，41-74).无论先前治疗的数量如何，患者对拉罗列替尼反应良好。不良事件（AE）大多为1/2级。15例（42%）患者发生3级治疗紧急AE（TEAE）。没有4级TEAE。报告了两个5级TEAE，两者均未被认为与拉罗列替尼有关.4名（11%）患者因TEAE而永久停止治疗。
结论：拉罗替尼表现出稳健和持久的反应，延长生存获益，并且在随访时间较长的TRK融合肉瘤成年患者中具有良好的安全性。这些结果继续表明，NTRK基因融合的测试应纳入患有各种类型肉瘤的成年患者的临床治疗中。
结论：原肌球蛋白受体激酶（TRK）融合蛋白是由涉及NTRK基因的易位引起的，并在一系列肿瘤类型中引起癌症。Larotrectinib是一种特异性靶向TRK融合蛋白的药物，被批准用于治疗TRK融合癌患者。这项研究观察了larotrectinib在TRK融合蛋白引起的肉瘤成年患者中的作用。超过一半的患者对larotrectinib有持久的反应，没有意想不到的副作用。这些结果表明，拉罗替尼对TRK融合肉瘤的成年患者是安全有效的。
方法：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）。患者每天两次口服larotrectinib100mg。响应是根据RECISTv1.1的研究者评估的。数据截止日期为2021年7月20日。
结果：在数据截止处，36名TRK融合肉瘤的成人患者开始了larotrectinib治疗：两名（6％）患者患有骨肉瘤，四个（11%）有胃肠道间质瘤，30例（83％）有软组织肉瘤。所有患者均可评估反应，客观反应率为58%（95%置信区间，41-74).无论先前治疗的数量如何，患者对拉罗列替尼反应良好。不良事件（AE）大多为1/2级。15例（42%）患者发生3级治疗紧急AE（TEAE）。没有4级TEAE。报告了两个5级TEAE，两者均未被认为与拉罗列替尼有关.4名（11%）患者因TEAE而永久停止治疗。
结论：拉罗替尼表现出稳健和持久的反应，延长生存获益，并且在随访时间较长的TRK融合肉瘤成年患者中具有良好的安全性。这些结果继续表明，NTRK基因融合的测试应纳入患有各种类型肉瘤的成年患者的临床治疗中。
结论：原肌球蛋白受体激酶（TRK）融合蛋白是由涉及NTRK基因的易位引起的，并在一系列肿瘤类型中引起癌症。Larotrectinib是一种特异性靶向TRK融合蛋白的药物，被批准用于治疗TRK融合癌患者。这项研究观察了larotrectinib在TRK融合蛋白引起的肉瘤成年患者中的作用。超过一半的患者对larotrectinib有持久的反应，没有意想不到的副作用。这些结果表明，拉罗替尼对TRK融合肉瘤的成年患者是安全有效的。
