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克唑替尼与化疗在晚期ALK阳性肺癌中的疗效比较
Crizotinib versus Chemotherapy in Advanced ALK-Rearranged Lung Cancer


Alice T. Shaw ... 肿瘤 呼吸系统疾病 • 2013.06.20
相关阅读
• 对艾乐替尼和克唑替尼用于未经治疗的ALK阳性非小细胞肺癌的比较研究 • ASCO 2017报告——肺癌

摘要


背景

既往单组研究显示,间变性淋巴瘤激酶(ALK)基因的染色体重排与口服酪氨酸激酶抑制剂、ALK靶向药物克唑替尼的显著临床应答相关。然而我们仍不清楚克唑替尼的疗效是否优于标准化疗。


方法

我们开展了一项三期、开放试验,在347例接受过一次铂类药物治疗的局部进展或转移性ALK-阳性肺癌患者中比较了克唑替尼和化疗的疗效。患者经随机分组,分别每天口服2次克唑替尼(250 mg)或者每3周静脉注射一次培美曲塞(500 mg/m2)或者多西他赛(75 mg/m2)。作为另一项研究的一部分,化疗组患者出现疾病进展时,可以交叉进入克唑替尼治疗组。试验的主要研究终点是疾病无进展生存时间。


结果

克唑替尼及化疗组的中位无进展生存期分别为7.7个月和3.0个月(克唑替尼组疾病进展或死亡的危险比为0.49;95% CI为0.37~0.64;P<0.001)。克唑替尼组治疗缓解率为65%(95% CI为58~72),相比之下化疗组为20%(95% CI为14~26)(P<0.001)。总生存期中期分析结果显示,克唑替尼组相比化疗组没有明显改善(克唑替尼组疾病死亡的风险比为1.02;95% CI为0.68~1.54;P=0.540)。与克唑替尼相关的常见不良事件为视觉障碍、胃肠道副作用和肝脏转氨酶含量升高,而化疗的常见不良事件为疲劳、脱发和呼吸困难。与化疗组相比,克唑替尼组患者汇报肺癌症状得到更多缓解,整体生活质量也得到改善。


结论

对于曾经接受治疗的、ALK基因发生重排的晚期非小细胞肺癌患者,克唑替尼疗效优于标准化疗(由辉瑞[Pfizer]资助;ClinicalTrials.gov注册号为NCT00932893)。





作者信息

Alice T. Shaw, M.D., Ph.D., Dong-Wan Kim, M.D., Ph.D., Kazuhiko Nakagawa, M.D., Ph.D., Takashi Seto, M.D., Lucio Crinó, M.D., Myung-Ju Ahn, M.D., Tommaso De Pas, M.D., Benjamin Besse, M.D., Ph.D., Benjamin J. Solomon, M.B., B.S., Ph.D., Fiona Blackhall, M.D., Ph.D., Yi-Long Wu, M.D., Michael Thomas, M.D., Kenneth J. O'Byrne, M.D., Denis Moro-Sibilot, M.D., D. Ross Camidge, M.D., Ph.D., Tony Mok, M.D., Vera Hirsh, M.D., Gregory J. Riely, M.D., Ph.D., Shrividya Iyer, Ph.D., Vanessa Tassell, B.S., Anna Polli, B.S., Keith D. Wilner, Ph.D., and Pasi A. Jänne, M.D., Ph.D.
From Massachusetts General Hospital (A.T.S.) and Lowe Center for Thoracic Oncology and Belfer Institute for Applied Cancer Science, Dana–Farber Cancer Institute (P.A.J.), Boston; Seoul National University Hospital (D.-W.K.) and Sungkyunkwan University School of Medicine, Samsung Medical Center (M.-J.A.), Seoul, South Korea; Kinki University Faculty of Medicine, Osakasayama City, Osaka (K.N.), and National Kyushu Cancer Center, Fukuoka (T.S.) — both in Japan; Azienda Ospedale Perugia, Perugia (L.C.), and European Institute of Oncology (T.D.P.) and Pfizer Italia (A.P.), Milan — all in Italy; Institut Gustave Roussy, Villejuif (B.B.), and Thoracic Oncology Unit, Centre Hospitalier Universitaire Grenoble, Grenoble (D.M.-S.) — both in France; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.); Christie National Health Service Foundation Trust, Manchester, United Kingdom (F.B.); Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China (Y.-L.W.); Thoraxklinik im Universitätsklinikum Heidelberg, and Translational Lung Research Center Heidelberg (Member of German Center for Lung Research), Heidelberg, Germany (M.T.); ICORG, the All Ireland Cooperative Oncology Research Group, Dublin (K.J.O.); University of Colorado, Aurora (D.R.C.); Chinese University of Hong Kong, Shatin, China (T.M.); McGill University Health Centre, Montreal (V.H.); Memorial Sloan-Kettering Cancer Center (G.J.R.) and Pfizer Oncology (S.I.), New York; and Pfizer Oncology, La Jolla, CA (V.T., K.D.W.). Address reprint requests to Dr. Shaw at Massachusetts General Hospital Cancer Center, Yawkey 7B, 32 Fruit St., Boston, MA 02114, or at ashaw1@partners.org.

 

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