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Am J Manag Care. 2022 Jan;28(2 Suppl):S26-S32. doi: 10.37765/ajmc.2022.88845.
Larotrectinib and entrectinib are tumor-agnostic tropomyosin receptor kinase (TRK) inhibitors that are indicated for the treatment of advanced or metastatic solid tumor cancers with neurotrophic tyrosine receptor kinase (NTRK) gene fusions. Regulatory approval of both agents was based on data from single-arm phase 1/2 studies, including tumor-agnostic basket trials. In the absence of randomized controlled trials, there remains a paucity of data to demonstrate the comparative effectiveness of larotrectinib and entrectinib vs established standard-of-care treatments in cancers with NTRK gene fusions. Furthermore, no studies have directly compared the 2 agents. This article reviews what is known about the comparative effectiveness of larotrectinib and entrectinib vs standard therapies in TRK fusion cancer and examines the comparative effectiveness of the 2 TRK inhibitors. Historical and intrapatient comparisons suggest that TRK inhibitors improve disease response compared with preexisting treatments across most tumor histologies; indirect and limited comparisons of phase 1/2 data and preliminary simulation modeling suggest a potential advantage for larotrectinib over entrectinib in terms of clinical response and survival. Although limited, these data provide some insight into the position of these treatments in established treatment paradigms for TRK fusion cancer, a setting where real-world evidence will be slow to accrue due to the rare nature of these tumors but may be the only way in the future to answer the outstanding questions regarding these 2 agents. Meanwhile, we need to try to obtain the maximum benefit that can be achieved for our patients using the currently available knowledge.
拉罗替尼和恩曲替尼是肿瘤不可知论的原肌球蛋白受体激酶（TRK）抑制剂，适用于治疗具有神经营养酪氨酸受体激酶（NTRK）基因融合的晚期或转移性实体瘤癌症。这两种药物的监管批准基于来自单臂 1/2 期研究的数据，包括肿瘤不可知论的篮子试验。由于没有随机对照试验，仍然缺乏数据表明拉罗替尼和恩曲替尼在 NTRK 基因融合癌症中与既定标准治疗相比的比较有效性。此外，没有研究直接比较这两种药物。本文回顾了拉罗替尼和恩曲替尼与标准疗法在 TRK 融合癌症中的比较有效性，并检查了这两种 TRK 抑制剂的比较有效性。历史和患者内比较表明，TRK 抑制剂与大多数肿瘤组织学的现有治疗相比，改善了疾病反应；1/2 期数据的间接和有限比较以及初步模拟建模表明，拉罗替尼在临床反应和生存方面可能优于恩曲替尼。尽管数据有限，但这些数据为这些治疗在 TRK 融合癌症的既定治疗模式中的地位提供了一些见解，由于这些肿瘤的罕见性质，真实世界证据的积累将很缓慢，但这可能是未来回答关于这两种药物的未决问题的唯一方法。同时，我们需要尝试利用当前可用的知识为患者获得最大的收益。
