Paik Paul K, Iams Wade T, Husain Hatim, O'Hara Richard M, Adewusi Emmanuel, Le Xiuning
Department of Medicine, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Cancer Treat Rev. 2025 Jul 1;139:102990. doi: 10.1016/j.ctrv.2025.102990.
The management of non-small cell lung cancer (NSCLC) has been transformed by the identification of specific therapies which target oncogenic drivers, including MET exon 14 (METex14) skipping, which occurs in 3-4% of patients. The development of selective MET inhibitors, such as tepotinib, has provided much-needed oral, targeted treatment options for these patients who otherwise have poor outcomes. In the largest trial involving patients with METex14 skipping NSCLC, the Phase II VISION study, tepotinib demonstrated robust and durable efficacy, which was especially notable when used in the first-line setting. Subgroup analyses demonstrated consistent efficacy in older and younger patients, Asian patients, and patients with brain metastases. The trial supported initial approval of tepotinib in Japan in 2020 and later in the US (accelerated approval: 2021; full approval: 2024) and many other countries worldwide. Here we delve into published literature on tepotinib, overview the mechanism of action and pharmacology, and provide a deep-dive into data from the pivotal VISION study, examining long-term outcomes, insights relevant for treatment sequencing, and biomarker analyses. We also discuss real-world data for tepotinib, indirect comparisons versus immuno- and/or chemotherapy, and provide experience from clinical practice, including guidance on managing adverse events, to provide a valuable aid for clinical practitioners.
非小细胞肺癌（NSCLC）的治疗因针对致癌驱动因素的特定疗法的发现而发生了变革，这些驱动因素包括MET外显子14（METex14）跳跃，在3%-4%的患者中出现。选择性MET抑制剂（如替泊替尼）的开发为这些预后不佳的患者提供了急需的口服靶向治疗选择。在涉及METex14跳跃NSCLC患者的最大规模试验——II期VISION研究中，替泊替尼显示出强大而持久的疗效，在一线治疗中使用时尤为显著。亚组分析表明，在老年和年轻患者、亚洲患者以及脑转移患者中疗效一致。该试验支持替泊替尼于2020年在日本首次获批，随后在美国获批（加速批准：2021年；完全批准：2024年）以及全球许多其他国家获批。在此，我们深入研究关于替泊替尼的已发表文献，概述其作用机制和药理学，并深入探讨关键VISION研究的数据，审视长期疗效、与治疗顺序相关的见解以及生物标志物分析。我们还讨论替泊替尼的真实世界数据、与免疫治疗和/或化疗的间接比较，并提供临床实践经验，包括不良事件管理指南，为临床医生提供有价值的帮助。
