法国古斯塔夫·鲁西研究所Karim Fizazi团队研究了达洛鲁胺治疗非转移性、去势抵抗性前列腺癌患者的生存率。2020年9月10日，该研究发表在《新英格兰医学杂志》上。

达洛鲁胺是一种结构独特的雄激素受体抑制剂，被批准用于治疗非转移性、去势抵抗性的前列腺癌。在先前的3期临床试验的初步分析中，使用达洛鲁胺治疗的中位无转移生存期为40.4个月，显著长于安慰剂治疗的18.4个月，但当时用于总体生存率分析的数据尚不成熟。

在这项双盲、安慰剂对照试验中，研究组招募了1509名非转移性、去势抵抗性前列腺癌男性患者，将其按2：1随机分配，其中955名接受达洛鲁胺治疗，554名接受安慰剂治疗，同时两组均继续接受雄激素剥夺治疗。当主要终点疗效明确后，安慰剂组患者可交叉接受开放标签的达洛鲁胺治疗。

中位随访29.0个月后，在解除双盲时，仍在接受安慰剂治疗的170名患者全部转用达洛鲁胺治疗。达洛鲁胺组的3年总生存率为83%，安慰剂组为77%。达洛鲁胺组的死亡风险比安慰剂组降低31%，差异显著。达洛鲁胺组的其他次要终点，包括首次出现症状性骨骼事件的时间和首次使用细胞毒性化疗的时间，均显著优于安慰剂组。两组患者的不良事件发生率相差不大，未发生新的安全事件。

总之，对于无转移性、去势抵抗性的前列腺癌患者，接受达洛鲁胺治疗的3年生存率显著高于安慰剂治疗，且安全性好。

附：英文原文

Title: Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide

Author: Karim Fizazi, M.D.,, Neal Shore, M.D.,, Teuvo L. Tammela, M.D., Ph.D.,, Albertas Ulys, M.D.,, Egils Vjaters, M.D.,, Sergey Polyakov, M.D.,, Mindaugas Jievaltas, M.D.,, Murilo Luz, M.D.,, Boris Alekseev, M.D.,, Iris Kuss, M.D.,, Marie-Aude Le Berre, M.Sc.,, Oana Petrenciuc, M.D.,, Amir Snapir, M.D., Ph.D.,, Toni Sarapohja, M.Sc.,, and Matthew R. Smith, M.D., Ph.D.

Issue&Volume: 2020-09-10

Abstract:

Background

Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.4 months). The data for the analysis of overall survival were immature at the time of the primary analysis.

Methods

In this double-blind, placebo-controlled trial, we randomly assigned 1509 men, in a 2:1 ratio, to receive darolutamide (955 patients) or placebo (554 patients) while they continued to receive androgen-deprivation therapy. After the results of the primary end-point analysis were found to be positive, unblinding of the treatment assignments occurred, and patients in the placebo group were permitted to cross over to receive open-label darolutamide treatment. At the time of this prespecified final analysis, which had been planned to be performed after approximately 240 deaths had occurred, overall survival and all other secondary end points were evaluated.

Results

The median follow-up time was 29.0 months. At the time of unblinding of the data, all 170 patients who were still receiving placebo crossed over to receive darolutamide; 137 patients who had discontinued placebo before unblinding had occurred received at least one other life-prolonging therapy. Overall survival at 3 years was 83% (95% confidence interval [CI], 80 to 86) in the darolutamide group and 77% (95% CI, 72 to 81) in the placebo group. The risk of death was significantly lower, by 31%, in the darolutamide group than in the placebo group (hazard ratio for death, 0.69; 95% CI, 0.53 to 0.88; P=0.003). Darolutamide was also associated with a significant benefit with respect to all other secondary end points, including the time to first symptomatic skeletal event and the time to first use of cytotoxic chemotherapy. The incidence of adverse events after the start of treatment was similar in the two groups; no new safety signals were observed.

Conclusions

Among men with nonmetastatic, castration-resistant prostate cancer, the percentage of patients who were alive at 3 years was significantly higher among those who received darolutamide than among those who received placebo. The incidence of adverse events was similar in the two groups.

DOI: 10.1056/NEJMoa2001342

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2001342