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特泊替尼治疗MET外显子14跳跃突变的非小细胞肺癌
Tepotinib in Non–Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations


Paul K. Paik ... 肿瘤 • 2020.09.03
相关阅读
• 晚期非小细胞肺癌的精确诊断和治疗 • 患者整个癌症病程中的基因组测序 • 追踪非小细胞肺癌的进化

VISION研究为MET突变非小细胞肺癌带来新愿景

 

蒋京伟

上海嘉会国际肿瘤中心

 

就在本月初,美国食品药品管理局(FDA)批准了首个特异性针对MET外显子14(MET exon-14)跳跃突变的MET抑制剂capmatinib用于一线及后线治疗携带该突变的非小细胞肺癌(NSCLC)。

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摘要


背景

3%~4%的非小细胞肺癌(NSCLC)患者发生剪接位点突变,导致致癌驱动基因MET外显子14出现转录丢失。我们评估了高选择性MET抑制剂特泊替尼(tepotinib)在该患者人群中的疗效和安全性。

 

方法

在这项开放标签的2期研究中,经确认携带MET外显子14跳跃突变的晚期或转移性NSCLC患者接受了特泊替尼治疗(剂量为每日一次,每次500 mg)。主要终点是经过独立审核,接受至少9个月随访的患者的客观缓解率。我们根据液体活检或组织活检是否检出MET外显子14跳跃突变来分析缓解率。

 

结果

截至2020年1月1日,共计152例患者接受了特泊替尼治疗,99例患者接受了至少9个月随访。独立审核委员会判定合并活检组的缓解率为46%(95%置信区间[CI],36~57),中位缓解持续时间为11.1个月(95% CI,7.2到无法估计)。液体活检组66例患者的缓解率为48%(95% CI,36~61);组织活检组60例患者的缓解率为50%(95% CI,37~63);两种活检方法均呈阳性的患者有27例。研究者判定的缓解率为56%(95% CI,45~66),且无论之前针对晚期或转移性肺癌接受过何种治疗方案,缓解率均相似。研究者认为与特泊替尼治疗相关的3级或更高级别不良事件发生率为28%,其中外周水肿发生率为7%。11%的患者发生了导致特泊替尼永久性停药的不良事件。我们通过检测血循环中的游离DNA判断分子学缓解状态;在基线和治疗期间有匹配的液体活检样本患者中,我们观察到67%的患者达到分子学缓解。

 

结论

在经确认携带MET外显子14跳跃突变的晚期NSCLC患者中,特泊替尼治疗与约一半患者达到缓解相关。外周水肿是主要的3级或更高级别毒性反应(由默克公司[德国达姆施塔特市]资助,VISION试验在ClinicalTrials.gov注册号为NCT02864992)。





作者信息

Paul K. Paik, M.D., Enriqueta Felip, M.D., Ph.D., Remi Veillon, M.D., Hiroshi Sakai, M.D., Alexis B. Cortot, M.D., Ph.D., Marina C. Garassino, M.D., Julien Mazieres, M.D., Ph.D., Santiago Viteri, M.D., Helene Senellart, M.D., Jan Van Meerbeeck, M.D., Ph.D., Jo Raskin, M.D., Niels Reinmuth, M.D., Ph.D., Pierfranco Conte, M.D., Dariusz Kowalski, M.D., Ph.D., Byoung Chul Cho, M.D., Ph.D., Jyoti D. Patel, M.D., Leora Horn, M.D., Frank Griesinger, M.D., Ph.D., Ji-Youn Han, M.D., Ph.D., Young-Chul Kim, M.D., Ph.D., Gee-Chen Chang, M.D., Ph.D., Chen-Liang Tsai, M.D., James C.-H. Yang, M.D., Ph.D., Yuh-Min Chen, M.D., Ph.D., Egbert F. Smit, M.D., Ph.D., Anthonie J. van der Wekken, M.D., Ph.D., Terufumi Kato, M.D., Dilafruz Juraeva, Ph.D., Christopher Stroh, Ph.D., Rolf Bruns, M.Sc., Josef Straub, Ph.D., Andreas Johne, M.D., Jürgen Scheele, M.D., Ph.D., John V. Heymach, M.D., Ph.D., and Xiuning Le, M.D., Ph.D.
From Memorial Sloan Kettering Cancer Center, New York (P.K.P.); the Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (E.F.), and Dr. Rosell Oncology Institute, Dexeus University Hospital, Quirónsalud Group (S.V.), Barcelona; Centre Hospitaliere Universitaire (CHU) Bordeaux, Service des Maladies Respiratoires, Bordeaux (R.V.), Université de Lille, CHU Lille, Thoracic Oncology Department, Centre National de la Recherche Scientifique, INSERM, Institut Pasteur de Lille, UMR9020–UMR-S 1277–Canther, Lille (A.B.C.), CHU de Toulouse, Institut Universitaire du Cancer de Toulouse, Université Paul Sabatier, Toulouse (J.M.), and Institut de Cancérologie de l’Ouest Rene Gauducheau Centre, Saint-Herblain (H. Senellart) — all in France; Saitama Cancer Center, Saitama (H. Sakai), and the Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama (T.K.) — both in Japan; the Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (M.C.G.), and the Department of Surgery, Oncology and Gastroenterology, University of Padua and Oncologia Medica 2, Istituto Oncologico Veneto, IRCCS, Padua (P.C.) — both in Italy; Antwerp University Hospital, Edegem, Belgium (J.V.M., J.R.); Asklepios Lung Clinic, Munich-Gauting (N.R.), Pius Hospital Oldenburg, University Medicine Oldenburg, Oldenburg (F.G.), Translational Medicine, Department of Bioinformatics (D.J.), Translational Innovation Platform, Oncology (C.S.), the Department of Biostatistics (R.B.), Translational Medicine, Department of Clinical Biomarkers and Companion Diagnostics (J. Straub), and Global Clinical Development (A.J., J. Scheele), Merck, Darmstadt — all in Germany; the Department of Lung Cancer and Thoracic Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (D.K.); Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), the Center for Lung Cancer, National Cancer Center, Goyang (J.-Y.H.), and Chonnam National University Medical School and Hwasun Hospital, Hwasun (Y.-C.K.) — all in South Korea; Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago (J.D.P.); the Department of Medicine, Vanderbilt Ingram Cancer Center, Nashville (L.H.); the Faculty of Medicine, School of Medicine, National Yang-Ming University (G.-C.C.), the Division of Chest Medicine, Department of Internal Medicine, Tri-service General Hospital, National Defense Medical Center (C.-L.T.), National Taiwan University Hospital (J.C.-H.Y.), and the Department of Chest Medicine, Taipei Veterans General Hospital, and School of Medicine, National Yang-Ming University (Y.-M.C.), Taipei, and the Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung (G.-C.C.) — both in Taiwan; the Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (E.F.S.), and the Department of Pulmonology, University of Groningen and University Medical Center Groningen, Groningen (A.J.W.) — both in the Netherlands; and M.D. Anderson Cancer Center, University of Texas, Houston (J.V.H., X.L.). Address reprint requests to Dr. Paik at the Memorial Sloan Kettering Cancer Center, 530 E. 74th St., New York, NY 10065, or at paikp@mskcc.org.

 

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