在 PREVAIL 试验中，内脏疾病部位对接受恩杂鲁胺治疗的转移性去势抵抗性前列腺癌患者结局的影响。

Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial.

机构信息

OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR.

Department of Medical Oncology, Guy's Hospital, London, UK.

出版信息

Clin Genitourin Cancer. 2017 Oct;15(5):610-617.e3. doi: 10.1016/j.clgc.2017.02.007. Epub 2017 Mar 3.

DOI:10.1016/j.clgc.2017.02.007

PMID:28344102

Abstract

BACKGROUND

The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy.

PATIENTS AND METHODS

Prespecified analyses examined the coprimary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) only. All other efficacy analyses were post hoc. The visceral subgroup was divided into liver or lung subsets. Patients with both liver and lung metastases were included in the liver subset.

RESULTS

Of the 1717 patients in PREVAIL, 204 (12%) had visceral metastases at screening (liver only or liver/lung metastases, n = 74; lung only metastases, n = 130). In patients with liver metastases, enzalutamide was associated with an improvement in rPFS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22-0.90) but not OS (HR, 1.04; 95% CI, 0.57-1.87). In patients with lung metastases only, the HR for rPFS (0.14; 95% CI, 0.06-0.36) and the HR for OS (0.59; 95% CI, 0.33-1.06) favored enzalutamide over placebo. Patients with liver metastases had worse outcomes than those with lung metastases, regardless of treatment. Enzalutamide was well tolerated in patients with visceral disease.

CONCLUSIONS

Enzalutamide is an active first-line treatment option for men with asymptomatic or mildly symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer and visceral disease. Patients with lung-only disease fared better than patients with liver disease, regardless of treatment.

摘要

背景

多国 3 期、随机、双盲、安慰剂对照的 MDV3100 口服疗效和安全性研究在化疗初治的转移性去势抵抗性前列腺癌患者中进行，这些患者在雄激素剥夺治疗失败后出现进展（PREVAIL）。该试验是独特的，因为它纳入了有内脏疾病的患者。本分析旨在描述 PREVAIL 中具有特定内脏疾病部位的男性亚组的结果，以帮助临床医生了解这些患者在化疗前对恩扎卢胺的反应。

患者和方法

预设分析仅检查了影像学无进展生存期（rPFS）和总生存期（OS）的主要终点。所有其他疗效分析均为事后分析。内脏亚组分为肝或肺亚组。筛选时有肝和肺转移的患者归入肝亚组。

结果

在 PREVAIL 的 1717 例患者中，204 例（12%）在筛选时存在内脏转移（仅肝或肝/肺转移，n=74；仅肺转移，n=130）。在有肝转移的患者中，恩扎卢胺可改善 rPFS（风险比[HR]，0.44；95%置信区间[CI]，0.22-0.90），但不改善 OS（HR，1.04；95%CI，0.57-1.87）。仅肺转移的患者中，rPFS 的 HR（0.14；95%CI，0.06-0.36）和 OS 的 HR（0.59；95%CI，0.33-1.06）均有利于恩扎卢胺优于安慰剂。无论治疗如何，有肝转移的患者预后均比有肺转移的患者差。有内脏疾病的患者对恩扎卢胺耐受良好。