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厄达替尼治疗局部晚期或转移性尿路上皮细胞癌
Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma


Yohann Loriot ... 肿瘤 • 2019.07.25
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• ramucirumab治疗晚期尿路上皮癌 • 帕博利珠单抗治疗不宜用顺铂的晚期尿路上皮癌患者 • 阿特珠单抗治疗晚期尿路上皮癌

期中分析后从随机对照改单臂,尿路上皮癌新药试验

 

姜昊文*†;党永军‡

†复旦大学附属华山医院泌尿外科;‡复旦大学基础医学院

*通讯作者

 

尿路上皮癌发生于肾盂、输尿管、膀胱和尿道,是泌尿系统高发的恶性肿瘤。对于早期的临床病例,腔内微创手术切除或根治性手术联合辅助化疗,可以治愈或者控制疾病发展。

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摘要


背景

成纤维细胞生长因子受体编码基因(FGFR)改变在尿路上皮细胞癌中很常见,并且可能与对免疫干预的敏感性降低相关。厄达替尼(erdafitinib)是FGFR1-4的酪氨酸激酶抑制剂,在临床前模型和在纳入FGFR改变患者的1期研究中已表现出抗肿瘤活性。

 

方法

在这项开放标签的2期研究中,我们纳入了有预先规定的FGFR改变,且患局部晚期和不可切除或转移性尿路上皮细胞癌的患者。所有患者既往均在至少一个疗程的化疗期间或之后,或者在新辅助化疗或辅助化疗之后12个月内发生疾病进展。本试验允许患者既往接受过免疫治疗。我们最初将患者随机分组,分别在研究的剂量选择阶段以间断或连续用药方式接受厄达替尼治疗。根据期中分析,我们将连续用药方案的起始剂量设定为8 mg/d(选定方案组),并可在药效学指导下,将剂量增加至9 mg。主要终点是客观缓解率。关键次要终点包括无进展生存期、缓解持续时间和总生存期。

 

结果

选定方案组共有99例患者接受了中位5个周期的厄达替尼治疗。其中43%既往接受过至少2个疗程的治疗,79%有内脏转移,53%的肌酐清除率低于60 mL/min。厄达替尼治疗后,经证实的缓解率为40%(3%完全缓解,37%部分缓解)。在既往接受过免疫治疗的22例患者中,经证实的缓解率为59%。中位无进展生存期为5.5个月,中位总生存期为13.8个月。据报告,有46%的患者发生了3级或更高级别的治疗相关不良事件,主要通过剂量调整进行处理;13%的患者因不良事件停止治疗。无治疗相关死亡。

 

结论

在既往接受过治疗,有FGFR改变且患局部晚期和不可切除或转移性尿路上皮细胞癌的患者中,与厄达替尼用药相关的肿瘤客观缓解率为40%。据报告,有近一半的患者发生了3级或更高级别的治疗相关不良事件(由Janssen Research and Development资助;BLC2001在ClinicalTrials.gov注册号为NCT02365597)。





作者信息

Yohann Loriot, M.D., Andrea Necchi, M.D., Se Hoon Park, M.D., Jesus Garcia-Donas, M.D., Robert Huddart, M.C.R.P., Earle Burgess, M.D., Mark Fleming, M.D., Arash Rezazadeh, M.D., Begoña Mellado, M.D., Sergey Varlamov, M.D., Monika Joshi, M.D., Ignacio Duran, M.D., Scott T. Tagawa, M.D., Yousef Zakharia, M.D., Bob Zhong, Ph.D., Kim Stuyckens, M.Sc., Ademi Santiago-Walker, Ph.D., Peter De Porre, M.D., Anne O’Hagan, M.P.H., Anjali Avadhani, M.D., and Arlene O. Siefker-Radtke, M.D. for the BLC2001 Study Group*
From Gustave Roussy, INSERM Unité 981, Université Paris-Sud, Université Paris-Saclay, Villejuif, France (Y.L.); Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (A.N.); Sungkyunkwan University Samsung Medical Center, Seoul, South Korea (S.H.P.); Genitourinary and Gynecological Cancer Unit, Centro Integral Oncológico Clara Campal, Madrid (J.G.-D.), Hospital Clinic Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (B.M.), and Hospital Universitario Marques de Valdecilla, Santander (I.D.) — all in Spain; the Institute of Cancer Research, Sutton, London (R.H.); the Levine Cancer Institute, Atrium Health, Charlotte, NC (E.B.); Virginia Oncology Associates, US Oncology Research, Norfolk (M.F.); Norton Healthcare, Louisville, KY (A.R.); the Altai Regional Cancer Center, Barnaul, Russia (S.V.); the Penn State Cancer Institute, Hershey (M.J.), and Janssen Research and Development, Spring House (B.Z., A.S.-W., A.O., A.A.) — both in Pennsylvania; Weill Cornell Medical College, New York (S.T.T.); University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City (Y.Z.); Janssen Research and Development, Beerse, Belgium (K.S., P.D.P.); and the University of Texas M.D. Anderson Cancer Center, Houston (A.O.S.-R.). Address reprint requests to Dr. Siefker-Radtke at the University of Texas M.D. Anderson Cancer Center, 1155 Pressler St., Unit 1374, Houston, TX 77030, or at asiefker@mdanderson.org. *A list of investigators in the BLC2001 study is provided in the Supplementary Appendix, available at NEJM.org.

 

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