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劳拉替尼和克唑替尼用于晚期ALK阳性肺癌一线治疗的比较
First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer


Alice T. Shaw ... 肿瘤 • 2020.11.19
相关阅读
• 对阿来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 • 克唑替尼一线治疗与化疗在ALK阳性肺癌中的疗效比较 • 克唑替尼与化疗在晚期ALK阳性肺癌中的疗效比较

摘要


背景

劳拉替尼(lorlatinib)是第三代间变性淋巴瘤激酶(ALK)抑制剂,对既往经过治疗的ALK阳性非小细胞肺癌(NSCLC)患者有抗癌活性。劳拉替尼和克唑替尼用于晚期ALK阳性NSCLC一线治疗的疗效比较尚未明确。

 

方法

我们开展了一项全球性、随机、3期试验,本试验纳入了既往未因转移性疾病接受过全身性治疗的296例晚期ALK阳性NSCLC患者,并比较了劳拉替尼和克唑替尼的疗效。主要终点是通过盲法独立集中审核方式判定的无进展生存期。次要终点包括独立判定的客观缓解和颅内缓解。本试验预期的疾病进展或死亡事件数量为177起,计划在发生133起(75%)后对疗效进行期中分析。

 

结果

在劳拉替尼组和克唑替尼组中,12个月时存活且无疾病进展的患者百分比分别为78%(95%置信区间[CI],70~84)和39%(95% CI,30~48)(疾病进展或死亡的风险比,0.28;95% CI,0.19~0.41;P<0.001)。劳拉替尼组76%的患者(95% CI,68~83)和克唑替尼组58%的患者(95% CI,49~66)达到了客观缓解;在有可测量的脑转移的患者中,两组分别有82%(95% CI,57~96)和23%(95% CI,5~54)的患者达到了颅内缓解,劳拉替尼组71%的患者达到了颅内完全缓解。劳拉替尼组最常见的不良事件包括高脂血症、水肿、体重增加、周围神经病和认知受影响。劳拉替尼组的3级或4级不良事件(主要是血脂水平改变)数量超过克唑替尼组(72% vs. 56%)。两组分别有7%和9%的患者因不良事件停止治疗。

 

结论

在对既往未经治疗的晚期ALK阳性NSCLC患者的结果进行的期中分析中,劳拉替尼组患者的无进展生存期显著超过克唑替尼组,颅内缓解率也显著高于克唑替尼组。劳拉替尼组3级或4级不良事件的发生率高于克唑替尼组,原因是血脂水平改变的发生率高(由辉瑞资助,CROWN在ClinicalTrials.gov注册号为NCT03052608)。





作者信息

Alice T. Shaw, M.D., Ph.D., Todd M. Bauer, M.D., Filippo de Marinis, M.D., Ph.D., Enriqueta Felip, M.D., Ph.D., Yasushi Goto, M.D., Ph.D., Geoffrey Liu, M.D., Julien Mazieres, M.D., Ph.D., Dong-Wan Kim, M.D., Ph.D., Tony Mok, M.D., Anna Polli, B.Sc., Holger Thurm, M.D., Anna M. Calella, Ph.D., Gerson Peltz, M.D., M.P.H., and Benjamin J. Solomon, M.B., B.S., Ph.D. for the CROWN Trial Investigators*
From the Massachusetts General Hospital Cancer Center (A.T.S.) and Pfizer (G.P.) — both in Boston; Sarah Cannon Research Institute–Tennessee Oncology, Nashville (T.M.B.); European Institute of Oncology, IRCCS (F.M.), and Pfizer (A.P., A.M.C.) — both in Milan; Vall d’Hebron University Hospital and Institute of Oncology, International Oncology Bureau–Quirón, Barcelona (E.F.); National Cancer Center Hospital, Tokyo (Y.G.); Princess Margaret Cancer Centre, Toronto (G.L.); Toulouse University Hospital, Toulouse, France (J.M.); Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea (D.-W.K.); State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong (T.M.); Pfizer, La Jolla, CA (H.T.); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.). Address reprint requests to Dr. Shaw at the Massachusetts General Hospital Cancer Center, 32 Fruit St., Boston, MA 02114, or at: ashaw1@mgh.harvard.edu. *A complete list of the CROWN trial investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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