恩杂鲁胺治疗生化复发前列腺癌的疗效改善。

Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer.

机构信息

From the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles (S.J.F.); the Durham Veterans Affairs Health Care System, Durham, NC (S.J.F.); the Division of Urologic Oncology, Erasto Gaertner Hospital, Curitiba, Brazil (M.A.L.); IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Italy (U.D.G.); the Vancouver Prostate Centre, University of British Columbia, Vancouver (M.G.), and the Southern Alberta Institute of Urology, University of Calgary, Calgary (G.T.G.) - both in Canada; U.S. Urology Partners and Associated Medical Professionals of New York, Syracuse (C.M.P.); Global Development (G.P.H.) and Biostatistics (J.S.), Astellas Pharma, Northbrook, IL; Ewha Womans University Mokdong Hospital, Seoul, South Korea (C.-S.K.); Servicio de Urología, Fundación Instituto Valenciano de Oncología, Valencia, Spain (M.R.-B.); the Department of Urology and Research Program in Systems Oncology, University of Helsinki, and Helsinki University Hospital - both in Helsinki, Finland (A.R.); Global Product Development, Pfizer, Collegeville, PA (J.T.); the Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW (S.S.), the Prostate Centre of Excellence, Sydney Adventist Hospital, Sydney, NSW (H.H.W.), and the College of Health and Medicine, Australian National University, Canberra, ACT (H.H.W.) - all in Australia; Global Product Development, Pfizer, San Francisco (Y.T.); Chesapeake Urology Research Associates, Towson, MD (R.F.T.); the Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, United Kingdom (B.V.); the Department of Urology, University of Lille, Claude Huriez Hospital, Centre Hospitalier Universitaire Lille, Lille, France (A.V.); Global Product Development, Pfizer, Cambridge, MA (F.Z.); and the Carolina Urologic Research Center and GenesisCare US, Myrtle Beach, SC (N.D.S.).

出版信息

N Engl J Med. 2023 Oct 19;389(16):1453-1465. doi: 10.1056/NEJMoa2303974.

DOI:10.1056/NEJMoa2303974

PMID:37851874

Abstract

BACKGROUND

Patients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of enzalutamide plus androgen-deprivation therapy and enzalutamide monotherapy, as compared with androgen-deprivation therapy alone, are unknown.

METHODS

In this phase 3 trial, we enrolled patients with prostate cancer who had high-risk biochemical recurrence with a prostate-specific antigen doubling time of 9 months or less. Patients were randomly assigned, in a 1:1:1 ratio, to receive enzalutamide (160 mg) daily plus leuprolide every 12 weeks (combination group), placebo plus leuprolide (leuprolide-alone group), or enzalutamide monotherapy (monotherapy group). The primary end point was metastasis-free survival, as assessed by blinded independent central review, in the combination group as compared with the leuprolide-alone group. A key secondary end point was metastasis-free survival in the monotherapy group as compared with the leuprolide-alone group. Other secondary end points were patient-reported outcomes and safety.

RESULTS

A total of 1068 patients underwent randomization: 355 were assigned to the combination group, 358 to the leuprolide-alone group, and 355 to the monotherapy group. The patients were followed for a median of 60.7 months. At 5 years, metastasis-free survival was 87.3% (95% confidence interval [CI], 83.0 to 90.6) in the combination group, 71.4% (95% CI, 65.7 to 76.3) in the leuprolide-alone group, and 80.0% (95% CI, 75.0 to 84.1) in the monotherapy group. With respect to metastasis-free survival, enzalutamide plus leuprolide was superior to leuprolide alone (hazard ratio for metastasis or death, 0.42; 95% CI, 0.30 to 0.61; P<0.001); enzalutamide monotherapy was also superior to leuprolide alone (hazard ratio for metastasis or death, 0.63; 95% CI, 0.46 to 0.87; P = 0.005). No new safety signals were observed, with no substantial between-group differences in quality-of-life measures.

CONCLUSIONS

In patients with prostate cancer with high-risk biochemical recurrence, enzalutamide plus leuprolide was superior to leuprolide alone with respect to metastasis-free survival; enzalutamide monotherapy was also superior to leuprolide alone. The safety profile of enzalutamide was consistent with that shown in previous clinical studies, with no apparent detrimental effect on quality of life. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.).

摘要

背景

前列腺癌患者生化复发风险较高，进展风险增加。与单独去势治疗相比，恩扎卢胺联合去势治疗和恩扎卢胺单药治疗的疗效和安全性尚不清楚。

方法

在这项 3 期临床试验中，我们招募了前列腺特异性抗原倍增时间为 9 个月或更短的生化复发高风险的前列腺癌患者。患者以 1:1:1 的比例随机分配，接受恩扎卢胺（160mg）每日联合亮丙瑞林每 12 周（联合组）、安慰剂联合亮丙瑞林（亮丙瑞林单药组）或恩扎卢胺单药治疗（单药组）。主要终点是联合组与亮丙瑞林单药组相比无转移生存期的评估（由盲法独立中心审查）。主要次要终点是单药组与亮丙瑞林单药组相比无转移生存期。其他次要终点包括患者报告的结局和安全性。

结果

共有 1068 名患者接受了随机分组：355 名患者被分配至联合组，358 名患者被分配至亮丙瑞林单药组，355 名患者被分配至单药组。患者中位随访时间为 60.7 个月。5 年时，联合组无转移生存率为 87.3%（95%置信区间[CI]，83.0 至 90.6），亮丙瑞林单药组为 71.4%（95% CI，65.7 至 76.3），单药组为 80.0%（95% CI，75.0 至 84.1）。与亮丙瑞林单药相比，恩扎卢胺联合亮丙瑞林治疗具有更高的无转移生存率（转移或死亡的风险比，0.42；95%CI，0.30 至 0.61；P<0.001）；与亮丙瑞林单药相比，恩扎卢胺单药治疗也具有更高的无转移生存率（转移或死亡的风险比，0.63；95%CI，0.46 至 0.87；P=0.005）。未观察到新的安全性信号，各组间生活质量测量指标无明显差异。