Hallick John, Baird Anne-Marie, Falchook Gerald, Le Xiuning, Hong David, Viteri Santiago, Raskin Jo, Reinmuth Niels, Vlassak Soetkin, Militaru Mihaela, Paik Paul K
Patient author, MET Crusaders, USA.
Trinity Translational Medicine Institute, Trinity College, University of Dublin, Ireland.
Future Oncol. 2023 Mar;19(10):683-696. doi: 10.2217/fon-2022-1035. Epub 2023 Mar 31.
WHAT IS THIS SUMMARY ABOUT?: This plain language summary provides an overview of two of the main clinical studies that led to tepotinib's approval, the phase I first-in-human study and the phase II VISION study.
WHAT IS TEPOTINIB?: Tepotinib is a targeted anti-cancer treatment taken orally (by mouth). It is available in many countries for people with advanced or metastatic non-small cell lung cancer (NSCLC), where the tumor contains a genetic mutation (alteration) called ' exon 14 skipping'. Tumor cells rely on this mutation to grow and survive, so targeted blocking of the effect of this mutation is an important treatment approach. exon 14 skipping occurs in approximately 3-4% of people with NSCLC. These people are usually of older age. This subtype of NSCLC is associated with poor outcomes. Before treatments that specifically target this mutation were developed, only general treatments such as chemotherapy were available for this type of cancer. Because chemotherapy attacks all rapidly dividing cells in a person's body and is administered intravenously (through a vein), it can often cause unwanted side effects. Cancer cells grow and divide rapidly because of defects, often involving proteins called 'tyrosine kinases'. Specific tyrosine kinase inhibitors (TKIs) were therefore developed to slow or stop cancer growth by targeting these proteins. Tepotinib is a MET TKI. This means that it blocks the activity of the MET pathway that is overactive in exon 14 skipping NSCLC. Doing this, may slow down cancer growth.
WHAT WERE THE RESULTS FROM THE CLINICAL STUDIES OF TEPOTINIB?: In the studies summarized here, people with exon 14 skipping NSCLC who took tepotinib had their tumor growth stopped or their tumor shrunk for a period of time, and they mostly experienced side effects that they could tolerate. : NCT01014936 (tepotinib first-in-human), NCT02864992 (VISION), NCT03940703 (INSIGHT 2) (ClinicalTrials.gov).
本摘要的内容是什么？：本通俗易懂的摘要概述了两项促成替泊替尼获批的主要临床研究，即I期首次人体研究和II期VISION研究。
什么是替泊替尼？：替泊替尼是一种口服的靶向抗癌治疗药物。在许多国家，它适用于患有晚期或转移性非小细胞肺癌（NSCLC）且肿瘤存在一种名为“外显子14跳跃”的基因突变（改变）的患者。肿瘤细胞依赖这种突变来生长和存活，因此针对性地阻断这种突变的作用是一种重要的治疗方法。外显子14跳跃发生在约3% - 4%的NSCLC患者中。这些患者通常年龄较大。这种NSCLC亚型预后较差。在开发出专门针对这种突变的治疗方法之前，针对这类癌症只有化疗等常规治疗手段。由于化疗会攻击人体中所有快速分裂的细胞且通过静脉注射给药，它常常会引发不良副作用。癌细胞由于缺陷（通常涉及称为“酪氨酸激酶”的蛋白质）而快速生长和分裂。因此，人们开发了特定的酪氨酸激酶抑制剂（TKIs），通过靶向这些蛋白质来减缓或阻止癌症生长。替泊替尼是一种MET TKI。这意味着它可阻断在具有外显子14跳跃的NSCLC中过度活跃的MET通路。这样做可能会减缓癌症生长。
替泊替尼的临床研究结果如何？：在此总结的研究中，患有外显子14跳跃NSCLC且服用替泊替尼的患者，其肿瘤生长停止或肿瘤在一段时间内缩小，并且他们大多经历了可耐受的副作用。：NCT01014936（替泊替尼首次人体研究）、NCT02864992（VISION）、NCT03940703（INSIGHT 2）（ClinicalTrials.gov）。
