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镥-177-PSMA-617治疗转移性去势抵抗性前列腺癌
Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer


Oliver Sartor ... 肿瘤 • 2021.09.16
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• 转移性前列腺癌的恩杂鲁胺联合标准一线治疗

表型精准医学的突破:放射配体疗法改善转移性去势抵抗性前列腺癌生存

 

韩星敏*,王瑞华,许莎莎

郑州大学第一附属医院核医学科;河南省分子影像医学重点实验室

*通讯作者

 

前列腺癌已成为泌尿系统发病率最高的肿瘤,2020年在男性恶性肿瘤中的发病率和死亡率分别位居第2位和第5位1。局部晚期或转移性前列腺癌接受雄激素剥夺治疗后,多数患者约在1年内进展为去势抵抗性前列腺癌或mCRPC。mCRPC是前列腺癌恶性进展的最后阶段,是前列腺癌致死的主要原因;患者的预后较差,总生存期不到2年。

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摘要


背景

转移性去势抵抗性前列腺癌的治疗虽然近期取得了一些进展,但该疾病仍具有致死性。前列腺特异性膜抗原(PSMA)在转移性去势抵抗性前列腺癌中高表达。镥-177(177Lu)-PSMA-617是可将β粒子辐射递送到表达PSMA的细胞和周围微环境的放射配体疗法。

 

方法

我们开展了一项国际性、开放标签、3期试验,目的是在接受过至少一种雄激素受体通路抑制剂和一种或两种紫杉类药物治疗,并且镓-68(68Ga)标记的PSMA-11正电子发射断层扫描-计算机断层扫描显示PSMA阳性的转移性去势抵抗性前列腺癌患者中评估177Lu-PSMA-617。我们以2∶1的比例将患者随机分组,两组分别接受177Lu-PSMA-617(每6周7.4 GBq,治疗4~6个周期)+研究方案允许的标准治疗或者单独标准治疗。研究方案允许的标准治疗不包括化疗、免疫治疗、镭-223(223Ra)和在研药物。备选主要终点(alternate primary end point)是影像学无进展生存期和总生存期;对于这两项,本试验的统计学功效分别足以检测出0.67和0.73的风险比。关键次要终点包括客观缓解、疾病控制和至发生有症状骨骼事件的时间。治疗期间的不良事件指的是末次给药后30日内且后续抗癌治疗之前发生的不良事件。

 

结果

从2018年6月至2019年10月中旬,在接受筛选的1,179例患者中,共计831例患者被随机分组。两组患者的基线特征平衡。中位随访时间为20.9个月。177Lu-PSMA-617+标准治疗与标准治疗相比显著延长了影像学无进展生存期(中位数,8.7个月vs. 3.4个月;进展或死亡的风险比,0.40;99.2% CI,0.29~0.57;P<0.001)和总生存期(中位数,15.3个月vs. 11.3个月;死亡的风险比,0.62;95% CI,0.52~0.74;P<0.001)。所有关键次要终点均表明177Lu-PSMA-617显著较优。使用177Lu-PSMA-617的情况下,3级或更高级别不良事件的发生率高于不使用177Lu-PSMA-617的情况(52.7% vs. 38.0%),但生活质量未受到不良影响。

 

结论

在晚期PSMA阳性转移性去势抵抗性前列腺癌患者中,标准治疗联用放射配体疗法177Lu-PSMA-617延长了影像学无进展生存期和总生存期(由Endocyte[诺华集团的公司]资助,VISION在ClinicalTrials.gov注册号为NCT03511664)。





作者信息

Oliver Sartor, M.D., Johann de Bono, M.B., Ch.B., Ph.D., Kim N. Chi, M.D., Karim Fizazi, M.D., Ph.D., Ken Herrmann, M.D., Kambiz Rahbar, M.D., Scott T. Tagawa, M.D., Luke T. Nordquist, M.D., Nitin Vaishampayan, M.D., Ghassan El-Haddad, M.D., Chandler H. Park, M.D., Tomasz M. Beer, M.D., Alison Armour, M.B., Ch.B., M.D., Wendy J. Pérez-Contreras, M.P.A., Michelle DeSilvio, Ph.D., Euloge Kpamegan, Ph.D., Germo Gericke, M.D., Ph.D., Richard A. Messmann, M.D., M.H.S., Michael J. Morris, M.D., and Bernd J. Krause, M.D. for the VISION Investigators*
From the School of Medicine, Tulane University, New Orleans (O.S.); the Institute of Cancer Research and Royal Marsden Hospital, London (J.B.); the British Columbia Cancer Agency, Vancouver, Canada (K.N.C.); Gustave Roussy Institute, Paris-Saclay University, Villejuif, France (K.F.); the University of Duisberg–Essen and German Cancer Consortium, University Hospital Essen, Essen (K.H.), University Hospital Münster, Münster (K.R.), and Rostock University Medical Center, Rostock (B.J.K.) — all in Germany; Weill Cornell Medicine (S.T.T.) and Memorial Sloan Kettering Cancer Center (M.J.M.) — both in New York; the Urology Cancer Center, Omaha, NE (L.T.N.); the School of Medicine, Wayne State University, Detroit (N.V.); Moffitt Cancer Center and Research Institute, Tampa, FL (G.E.-H.); Norton Cancer Institute, Louisville, KY (C.H.P.); Knight Cancer Institute, Oregon Health and Science University, Portland (T.M.B.); Endocyte (a Novartis company), West Lafayette, IN (A.A.); Novartis Pharmaceuticals, East Hanover, NJ (W.J.P.-C., M.D., E.K., R.A.M.); and Novartis Pharma, Basel, Switzerland (G.G.). Address reprint requests to Dr. Sartor at Tulane Cancer Center, School of Medicine, Tulane University, New Orleans, LA 70112, or at osartor@tulane.edu. *The list of the VISION investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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