Cardinal Health, Dublin, Ohio, USA.
Bayer Pharmaceuticals LLC, Whippany, New Jersey, USA.
Target Oncol. 2022 Sep;17(5):549-561. doi: 10.1007/s11523-022-00909-7. Epub 2022 Sep 11.
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are present across various tumor types with an estimated overall prevalence of less than 1%. Tropomyosin receptor kinase inhibitors (TRKis) block the constitutively activated tyrosine receptor kinase (TRK) fusion protein produced in cancers with NTRK gene fusions (NTRK+) from downstream signaling. Many treatment guidelines now include TRKis as first-line (1L) or subsequent treatment options for TRK fusion cancer.
This study aimed to assess treatment patterns subsequent to a finding of NTRK+ status among patients with TRK fusion cancer.
This was a one-time, retrospective, multi-site patient chart abstraction by oncology practices in the USA from June to September 2020. US medical oncologists from the Oncology Provider Extended Network (OPEN) who had treated patients with NTRK+ advanced/metastatic solid tumors abstracted information into electronic case report forms (eCRFs) for adult patients with advanced/metastatic solid tumors and a NTRK+ tumor test result with a known fusion partner. Data abstracted into eCRFs by oncologists included demographic, clinical, and treatment characteristics of patients with advanced/metastatic TRK fusion solid tumors. Responses were summarized using descriptive statistics. Median treatment durations across the lines of therapy were estimated by Kaplan-Meier time to discontinuation.
A total of 19 medical oncologists abstracted data from 110 patient charts. Median patient age at advanced/metastatic diagnosis was 62 years. The majority of patients were male (58.2%) and White (79.1%). Solid tumor types reported in at least 10% of the study cohort were lung (24.5%), cholangiocarcinoma (13.6%), pancreatic (10.9%), and colorectal (10.0%). Results for patients with hepatobiliary cancers (i.e., cholangiocarcinoma, pancreatic cancer, hepatocellular carcinoma) and colorectal cancer, and appendiceal cancer are also included. Median duration of 1L TRKi therapy was 16.8 months across all solid tumor types, whereas median duration of 1L was 5.6 months among patients receiving non-TRKi therapies (p = 0.017). Among the solid tumor types represented by at least 10% of the study population, median duration of 1L TRKi therapy was only reached in patients with pancreatic cancer (3.3 months). Median duration of TRKi in the second-line (2L) setting was 7.9 months overall, relative to 5.3 months among patients receiving non-TRKi therapies (p = 0.003). Across lung, cholangiocarcinoma, pancreatic, and colorectal cancers, the median durations of 2L TRKi therapy were 14.1, 6.0, 6.1, and 4.1 months, respectively.
Among patients with advanced/metastatic TRK fusion solid tumors, medical oncologists reported that approximately two-thirds initiated a TRKi during the study period. Treatment with a TRKi was longer in duration compared to non-TRKi treatment in 1L and 2L therapy. Additional research is needed to gain insight into the association between early TRKi therapy initiation and clinical outcomes in the real-world setting.
神经营养酪氨酸受体激酶(NTRK)基因融合存在于多种肿瘤类型中,总体患病率估计低于 1%。原肌球蛋白受体激酶抑制剂(TRKi)可阻断由 NTRK 基因融合(NTRK+)产生的癌症中组成性激活的酪氨酸受体激酶(TRK)融合蛋白的下游信号。许多治疗指南现在将 TRKi 作为 NTRK 融合癌的一线(1L)或后续治疗选择。
本研究旨在评估 NTRK+状态患者在接受 NTRK 融合癌治疗后的治疗模式。
这是一项由美国肿瘤实践进行的一次性、回顾性、多地点患者图表摘录,时间为 2020 年 6 月至 9 月。来自肿瘤提供者扩展网络(OPEN)的美国医学肿瘤学家摘录了患有 NTRK+晚期/转移性实体瘤的成年患者的电子病历报告表(eCRF)的信息,这些患者的肿瘤测试结果显示存在已知融合伴侣的 NTRK+肿瘤。肿瘤学家在 eCRF 中摘录的数据包括晚期/转移性 TRK 融合实体瘤患者的人口统计学、临床和治疗特征。使用描述性统计对反应进行总结。通过 Kaplan-Meier 时间至停药法估计各线治疗的中位治疗持续时间。
共有 19 名医学肿瘤学家从 110 份患者图表中摘录了数据。晚期/转移性诊断时患者的中位年龄为 62 岁。大多数患者为男性(58.2%)和白人(79.1%)。研究队列中至少有 10%报告的实体瘤类型为肺癌(24.5%)、胆管癌(13.6%)、胰腺癌(10.9%)和结直肠癌(10.0%)。也包括肝胆癌(即胆管癌、胰腺癌、肝细胞癌)和结直肠癌以及阑尾癌患者的结果。所有实体瘤类型中 1L TRKi 治疗的中位持续时间为 16.8 个月,而接受非 TRKi 治疗的患者中位持续时间为 5.6 个月(p=0.017)。在所代表的实体瘤类型中,至少有 10%的研究人群接受了胰腺肿瘤的 1L TRKi 治疗,中位持续时间仅达到 3.3 个月。总体而言,2L 设定中 TRKi 的中位治疗时间为 7.9 个月,而接受非 TRKi 治疗的患者为 5.3 个月(p=0.003)。在肺癌、胆管癌、胰腺癌和结直肠癌中,2L TRKi 治疗的中位持续时间分别为 14.1、6.0、6.1 和 4.1 个月。
在患有晚期/转移性 TRK 融合实体瘤的患者中,肿瘤学家报告称,研究期间约有三分之二的患者开始接受 TRKi 治疗。与非 TRKi 治疗相比,1L 和 2L 治疗中接受 TRKi 治疗的持续时间更长。需要进一步的研究来深入了解真实世界环境中早期 TRKi 治疗启动与临床结果之间的关联。