Department of Clinical Oncology, State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Hong Kong Cancer Institute and Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; Hong Kong Society of Uro-Oncology (HKSUO), Hong Kong.
Department of Clinical Oncology, State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Hong Kong Cancer Institute and Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; Hong Kong Society of Uro-Oncology (HKSUO), Hong Kong.
Clin Genitourin Cancer. 2018 Oct;16(5):402-412.e1. doi: 10.1016/j.clgc.2018.07.008. Epub 2018 Jul 21.
The present study retrospectively evaluated the efficacy and safety of enzalutamide in different lines of metastatic castration-resistant prostate cancer (mCRPC) treatment in a real-world setting.
The clinical records of patients with mCRPC treated with enzalutamide between August 2015 and October 2017 were retrieved from all 7 public oncology centers in Hong Kong and reviewed. The primary endpoint was progression-free survival (PFS) in first (1L), second (2L), and third or fourth lines (3L or 4L) of CRPC treatment. Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and tolerance.
Among a total of 117 patients (median age of 73 years [range, 52-90 years]), 34 (29.1%), 57 (48.7%), and 26 (19.3%) patients had enzalutamide as their 1L (chemo-naive), 2L (post-docetaxel or -abiraterone), and 3L or above treatment options. The overall PSA response rates were 43.6%, and were 73.5%, 35.1%, and 19.2% for 1L, 2L, and 3L or 4L treatment, respectively. PFS and OS were significantly associated with the line of treatment in the univariate survival analysis (1L/2L/3L and 4L; PFS, 7.1/3.9/2.2 months; OS, not reached/15.8/7.4 months; both P = .0002) but not in the multivariate analysis. The observed incidence of any fatigue (grade 1 or 2, 54.7%; grade 3 or 4, 9.4%) was much higher than reported in the AFFIRM (A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100 [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 34%) and PREVAIL (A Multinational Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy And Safety Study Of Oral Mdv3100 In Chemotherapy-naïve Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 36%) trials; as well, grade ≥ 2 fatigue was significantly associated with 3L or 4L treatment (P = .01 in both univariate and multivariate analyses).
In the real-life setting, there was a higher incidence of enzalutamide-related fatigue than reported in the trials. Earlier lines of enzalutamide treatment were associated with longer PFS and OS, more frequent PSA response, and less fatigue.
本研究回顾性评估了恩扎卢胺在真实世界环境下不同转移性去势抵抗性前列腺癌（mCRPC）治疗线中的疗效和安全性。
从香港所有 7 家公立肿瘤中心检索了 2015 年 8 月至 2017 年 10 月期间接受恩扎卢胺治疗的 mCRPC 患者的临床记录，并进行了回顾。主要终点为一线（1L）、二线（2L）和三线或四线（3L 或 4L）CRPC 治疗中的无进展生存期（PFS）。次要终点包括总生存期（OS）、前列腺特异性抗原（PSA）反应和耐受性。
在总共 117 名患者（中位年龄 73 岁[范围 52-90 岁]）中，34 名（29.1%）、57 名（48.7%）和 26 名（19.3%）患者的恩扎卢胺分别作为 1L（化疗初治）、2L（多西他赛或阿比特龙后）和 3L 或以上的治疗选择。总的 PSA 反应率为 43.6%，1L、2L 和 3L 或 4L 治疗的 PSA 反应率分别为 73.5%、35.1%和 19.2%。单变量生存分析显示，PFS 和 OS 与治疗线显著相关（1L/2L/3L 和 4L；PFS：7.1/3.9/2.2 个月；OS：未达到/15.8/7.4 个月；均 P=0.0002），但多变量分析中无相关性。任何等级的疲劳发生率（1 级或 2 级，54.7%；3 级或 4 级，9.4%）明显高于 AFFIRM（一项评估研究药物 MDV3100 疗效和安全性的研究[ClinicalTrials.gov 标识符：NCT00974311]）（任何等级，34%）和 PREVAIL（一项多中心 3 期、随机、双盲、安慰剂对照的研究，评估口服 MDV3100 在化疗初治的进展性转移性前列腺癌患者中的疗效和安全性，这些患者在接受雄激素剥夺治疗后出现进展[ClinicalTrials.gov 标识符：NCT00974311]）（任何等级，36%）试验中的报告；此外，≥2 级疲劳与 3L 或 4L 治疗显著相关（单变量和多变量分析中 P 值均为 0.01）。
在真实环境中，恩扎卢胺相关疲劳的发生率高于试验报告。早期的恩扎卢胺治疗与更长的 PFS 和 OS、更高的 PSA 反应和更少的疲劳相关。
