Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

被引：655

作者：

Beer, Tomasz M. ^{[1
]}

Kwon, Eugene D. ^{[2
]}

Drake, Charles G. ^{[3
]}

Fizazi, Karim ^{[4
]}

Logothetis, Christopher ^{[6
]}

Gravis, Gwenaelle ^{[5
]}

Ganju, Vinod ^{[7
]}

Polikoff, Jonathan ^{[10
]}

Saad, Fred ^{[11
]}

Humanski, Piotr ^{[12
]}

Piulats, Josep M. ^{[13
]}

Gonzalez Mella, Pablo ^{[15
,16
]}

Ng, Siobhan S. ^{[8
]}

Jaeger, Dirk ^{[17
]}

Parnis, Francis X. ^{[9
]}

Franke, Fabio A. ^{[18
]}

Puente, Javier ^{[14
]}

Carvajal, Roman ^{[19
]}

Sengelov, Lisa ^{[20
]}

McHenry, M. Brent ^{[21
]}

Varma, Arvind ^{[22
]}

van den Eertwegh, Alfonsus J. ^{[23
]}

Gerritsen, Winald ^{[24
]}

机构：

[1] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

[2] Mayo Clin, Rochester, MN USA

[3] Johns Hopkins Univ, Baltimore, MD USA

[4] Univ Paris Sud, Villejuif, France

[5] Inst Paoli Calmettes, Marseille, France

[6] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[7] Monash Univ, Melbourne, Vic, Australia

[8] St John God Hosp, Subiaco, WA, Australia

[9] Adelaide Canc Ctr, Adelaide, SA, Australia

[10] Southern Calif Permanente Med Grp, San Marcos, CA USA

[11] Ctr Hosp Univ Montreal, Montreal, PQ, Canada

[12] Niepubli Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland

[13] Inst Catal Oncol, Barcelona, Spain

[14] Hosp Clin San Carlos, Madrid, Spain

[15] Inst Oncol, Vina Del Mar, Chile

[16] Fdn Arturo Lopez Perez, Santiago, Chile

[17] Univ Hosp, Heidelberg, Germany

[18] Hosp Caridade Ijui, Ijui, Brazil

[19] Hosp Reg Valentin Gomez Farias, Zapopan, Mexico

[20] Herlev Hosp, Herlev, Denmark

[21] Bristol Myers Squibb, Wallingford, CT USA

[22] DOCS Inc, New York, NY USA

[23] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands

[24] Radboud Univ Nijmegen, Nijmegen, Netherlands

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2017年 / 35卷 / 01期

关键词：

ABIRATERONE ACETATE; SURVIVAL ANALYSIS; PLUS DACARBAZINE; ADVERSE EVENTS; OPEN-LABEL; MANAGEMENT; MELANOMA; RECOMMENDATIONS; IMMUNOTHERAPY; ENZALUTAMIDE;

D O I：

10.1200/JCO.2016.69.1584

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2: 1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in >= 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset. (C) 2016 by American Society of Clinical Oncology

引用

页码：40 / +

页数：12

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