美国威尔·康奈尔医学院Cora N. Sternberg团队探讨了恩杂鲁胺治疗非转移性、去势抵抗性前列腺癌对生存期的影响。2020年5月29日，《新英格兰医学杂志》发表了这一成果。

初步试验结果表明，恩杂鲁胺可显著改善接受雄激素剥夺治疗后的无转移、去势抵抗性前列腺癌、前列腺特异性抗原（PSA）水平迅速升高患者的无转移生存期。但总体生存最终分析的结果尚未报道。

在这项双盲、3期临床试验中，研究组招募继续接受雄激素剥夺治疗的非转移性、去势抵抗性前列腺癌患者，按2：1随机分配，其中933例接受恩杂鲁胺治疗，468例接受安慰剂治疗。

截至2019年10月15日，恩杂鲁胺组中有288例（31％）患者死亡，安慰剂组中有178例（38％）。恩杂鲁胺组的中位总生存期为67.0个月，安慰剂组为56.3个月，死亡风险比为0.73。恩杂鲁胺组校正后的3级及以上不良事件发生率为每100人年17例，而安慰剂组为每100人年20例。 恩杂鲁胺组的不良反应与此前报道一致。最频繁报告的事件是疲劳和肌肉骨骼事件。

总之，对于非转移性、去势抵抗性前列腺癌和PSA水平迅速升高的男性患者，恩杂鲁胺+雄激素剥夺疗法与安慰剂+雄激素剥夺疗法相比，显著延长了中位总生存期。恩杂鲁胺引起的死亡风险比安慰剂低27％，且未增加新的安全风险。

附：英文原文

Title: Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer | NEJM

Author: Cora N. Sternberg, M.D.,, Karim Fizazi, M.D., Ph.D.,, Fred Saad, M.D.,, Neal D. Shore, M.D.,, Ugo De Giorgi, M.D., Ph.D.,, David F. Penson, M.D., M.P.H.,, Ubirajara Ferreira, M.D., Ph.D.,, Eleni Efstathiou, M.D., Ph.D.,, Katarzyna Madziarska, M.D., Ph.D.,, Michael P. Kolinsky, M.D.,, Daniel I. G. Cubero, M.D., Ph.D.,, Bettina Noerby, M.D.,, Fabian Zohren, M.D., Ph.D.,, Xun Lin, Ph.D.,, Katharina Modelska, M.D., Ph.D.,, Jennifer Sugg, M.S.,, Joyce Steinberg, M.D.,, and Maha Hussain, M.D.

Issue&Volume: 2020-05-29

Abstract: Abstract

Background

Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported.

Methods

In this double-blind, phase 3 trial, men with nonmetastatic, castration-resistant prostate cancer (defined on the basis of conventional imaging and a PSA doubling time of ≤10 months) who were continuing to receive androgen-deprivation therapy were randomly assigned (in a 2:1 ratio) to receive enzalutamide at a dose of 160 mg or placebo once daily. Overall survival was assessed with a group sequential testing procedure and an O’Brien–Fleming–type alpha-spending function.

Results

As of October 15, 2019, a total of 288 of 933 patients (31%) in the enzalutamide group and 178 of 468 (38%) in the placebo group had died. Median overall survival was 67.0 months (95% confidence interval [CI], 64.0 to not reached) in the enzalutamide group and 56.3 months (95% CI, 54.4 to 63.0) in the placebo group (hazard ratio for death, 0.73; 95% CI, 0.61 to 0.89; P=0.001). The exposure-adjusted rate of adverse events of grade 3 or higher was 17 per 100 patient-years in the enzalutamide group and 20 per 100 patient-years in the placebo group. Adverse events in the enzalutamide group were consistent with those previously reported for enzalutamide; the most frequently reported events were fatigue and musculoskeletal events.

Conclusions

Enzalutamide plus androgen-deprivation therapy resulted in longer median overall survival than placebo plus androgen-deprivation therapy among men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level. The risk of death associated with enzalutamide was 27% lower than with placebo. Adverse events were consistent with the established safety profile of enzalutamide.

DOI: 10.1056/NEJMoa2003892

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2003892