在ROS1中的Repotrectinib 融合阳性非小细胞肺癌
Alexander Drilon1, D Ross Camidge1, Jessica J Lin1
1From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College (A.D.) and the NYU Perlmutter Cancer Center (V.V.) - all in New York; the University of Colorado, Anschutz Medical Campus, Aurora (D.R.C.); Massachusetts General Hospital, Harvard Medical School, Boston (J.J.L.); Asan Medical Center (S.-W.K.) and Yonsei Cancer Center, Yonsei University College of Medicine (B.C.C.), Seoul, and Chungbuk National University Hospital, Cheongju-si (K.H.L.) - all in South Korea; the Peter MacCallum Cancer Center, Melbourne, VIC (B.J.S.), and the Chris O'Brien Lifehouse, Camperdown, NSW (S.K.) - both in Australia; the Department of Oncology and Radiotherapy and Early Clinical Trials Center, Medical University of Gdansk, Gdansk, Poland (R.D.); Paris-Saclay University, Gustave Roussy Cancer Center, Villejuif (B.B.), and Centre Hospitalier Universitaire de Grenoble-Alpes, La Tronche (D.M.-S.) - both in France; National Cancer Center Hospital East, Kashiwa, Japan (K.G.); the Netherlands Cancer Institute, Amsterdam (A.J.L.); the Center for Integrated Oncology, University Hospital of Cologne, Cologne (J.W.), and the Department of Medical Oncology, Heidelberg University Hospital, National Center for Tumor Diseases, Heidelberg (C.S.) - both in Germany; the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London (S.P.), and the University of Manchester and the Christie NHS Foundation Trust, Manchester (M.G.K.) - all in the United Kingdom; the University of California, Irvine, School of Medicine, Orange (M.N.), and Turning Point Therapeutics, a wholly owned subsidiary of Bristol Myers Squibb, San Diego (S.S., M.M., D.T., A.G., G.S.) - both in California; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona (E.F.); Hunan Cancer Hospital, Hunan (N.Y.), the Department of Oncology, Shanghai Chest Hospital, Shanghai (S.L.), Sichuan Cancer Hospital and Institute, Chengdu (W.Y.), and Henan Cancer Hospital, Zhengzhou (X.H.) - all in China; the Respiratory Oncology Unit, University Hospitals Leuven, Leuven, Belgium (C.D.); UT Southwestern Medical Center, Dallas (M.S.B.); William Osler Health System, University of Toronto, Toronto (P.C.); and Bristol Myers Squibb, Princeton, NJ (Y.Y.).
雷波特雷克提尼布在ROS1融合阳性非小细胞肺癌 (NSCLC) 中表现出持久的临床活性,即使具有耐药性突变. 这种下一代氨酸激酶抑制剂 (TKI) 为晚期NSCLC患者提供了有前途的治疗选择.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 临床试验 临床试验
背景情况:
- 针对ROS1融合阳性非小细胞肺癌 (NSCLC) 的早期一代ROS1氨酸激酶抑制剂 (TKIs) 显示出抗瘤活性,但面临抗药性和次优 intracranial 疗效的挑战.
- 新一代ROS1TKI的Repotrectinib显示出对ROS1阳性癌症的临床前疗效,包括具有抗药性突变的癌症,如ROS1 G2032R.
研究的目的:
- 评估repotrectinib在患有晚期固体瘤的患者中的疗效和安全性,重点关注ROS1融合阳性NSCLC.
- 评估先前接受或未接受ROS1TKI治疗的患者,包括具有特定抗性突变的患者的repotrectinib的性能.
主要方法:
- 一项注册的1-2期临床试验,涉及患有晚期固体瘤的患者,包括ROS1融合阳性NSCLC.
- 主要疗效终点:确认客观反应. 二级终点:反应的持续时间,无进展的生存率和安全性.
- 疗效分析包括了试验的第一阶段和第二阶段的数据.
主要成果:
- 在之前未接受过治疗的ROS1阳性NSCLC患者中,repotrectinib实现了79%的客观反应率,反应的中位持续时间为34.1个月,中位无进展存活时间为35.7个月.
- 在先前用一种ROS1TKI (不使用化疗) 治疗的患者中,客观反应率为38%,反应的中位持续时间为14.8个月,中位无进展生存时间为9.0个月.
- 在具有ROS1 G2032R突变的患者中,59%的患者表现出反应. 常见的不良事件包括头,失眠症和麻醉症,由于与治疗相关的不良事件而导致的中止率较低.
结论:
- 雷波特雷克替尼在ROS1融合阳性NSCLC患者中表现出持久的临床活性,而不管之前的ROS1TKI治疗史.
- 雷波特雷克提尼布的不良事件概况通常是低级的和可控的,支持其长期管理的潜力.
- 这项名为TRIDENT-1 (NCT03093116) 的研究是由转折点治疗公司资助的.
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