Division of Hematology-Oncology, Durham VA Medical Center, Durham, NC.
Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC.
JCO Precis Oncol. 2023 Mar;7:e2200692. doi: 10.1200/PO.22.00692.
Neurotrophic tyrosine receptor kinase 1-3 () gene fusions are found in a broad range of tumor types. Clinical trials demonstrated high response rates to tropomyosin receptor kinase (TRK) inhibitors in fusion-positive cancers, but few reports have described real-world experience with these targeted agents. We evaluated the prevalence of fusions and the outcomes with TRK inhibitor therapy in a real-world population of patients in the Veterans Health Administration.
Patients with fusions or rearrangements were identified from the Veterans Affairs (VA) National Precision Oncology Program (NPOP), and patients who were prescribed TRK inhibitors were identified from the Corporate Data Warehouse. Baseline data and clinical outcomes were obtained by retrospective review of medical records.
A total of 33 patients with fusions or rearrangements were identified, including 25 patients comprising 0.12% of all patients with solid tumors sequenced through VA NPOP. Twelve patients with fusions or rearrangements were treated with TRK inhibitors, none of whom had objective responses. Eight patients experienced toxicities leading to drug interruption, dose reduction, or discontinuation.
In this retrospective study of VA patients, fusions and rearrangements were less common than in previous studies, and objective responses to TRK inhibitors were not observed. Real-world experience with TRK inhibitors differs markedly from clinical trial findings, possibly due to differences in patient demographics, tumor types, and sequencing methods. Our findings highlight the need to study TRK inhibitors in the real-world setting and in populations underrepresented in clinical trials.
神经营养酪氨酸受体激酶 1-3（）基因融合存在于广泛的肿瘤类型中。临床试验表明，在融合阳性癌症中，对原肌球蛋白受体激酶（TRK）抑制剂的反应率很高，但很少有报道描述这些靶向药物的真实世界经验。我们评估了退伍军人健康管理局（VA）真实世界人群中 TRK 抑制剂治疗的融合和结局的患病率。
从退伍军人事务部（VA）国家精准肿瘤学计划（NPOP）中确定了具有 融合或重排的患者，并从公司数据仓库中确定了接受 TRK 抑制剂治疗的患者。通过回顾性审查病历获得基线数据和临床结果。
共确定了 33 例具有 融合或重排的患者，其中包括 25 例患者，占通过 VA NPOP 对所有实体瘤患者进行测序的患者的 0.12%。12 例融合或重排患者接受了 TRK 抑制剂治疗，无客观缓解。8 例患者出现导致药物中断、剂量减少或停药的毒性。
在这项对 VA 患者的回顾性研究中，融合和重排比以前的研究少见，并且未观察到 TRK 抑制剂的客观反应。TRK 抑制剂的真实世界经验与临床试验结果明显不同，可能是由于患者人口统计学、肿瘤类型和测序方法的差异所致。我们的研究结果强调了在真实世界环境中和临床试验代表性不足的人群中研究 TRK 抑制剂的必要性。
