Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.
J Clin Oncol. 2017 Jan;35(1):40-47. doi: 10.1200/JCO.2016.69.1584. Epub 2016 Oct 31.
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.
依匹木单抗通过与细胞毒性 T 淋巴细胞相关抗原 4 结合来增强抗肿瘤 T 细胞反应。我们评估了在无内脏转移的化疗初治转移性去势抵抗性前列腺癌无症状或症状轻微的患者中使用依匹木单抗的治疗效果。
在这项多中心、双盲、III 期临床试验中，患者按 2:1 的比例随机分配（2:1）接受依匹木单抗 10mg/kg 或安慰剂每 3 周一次，最多 4 个剂量。非进展患者每 3 个月接受依匹木单抗 10mg/kg 或安慰剂维持治疗。主要终点是总生存期（OS）。
400 例患者被随机分配至依匹木单抗组，202 例患者被分配至安慰剂组；399 例患者接受了依匹木单抗治疗，199 例患者接受了安慰剂治疗。依匹木单抗组的中位 OS 为 28.7 个月（95%CI，24.5 至 32.5 个月），安慰剂组为 29.7 个月（95%CI，26.1 至 34.2 个月）（风险比，1.11；95.87%CI，0.88 至 1.39；P =.3667）。依匹木单抗组无进展生存期的中位时间为 5.6 个月，安慰剂组为 3.8 个月（风险比，0.67；95.87%CI，0.55 至 0.81）。探索性分析显示，依匹木单抗的前列腺特异性抗原反应率（23%）高于安慰剂组（8%）。依匹木单抗组报告的 10%以上患者出现腹泻（15%）等≥3 级治疗相关不良事件（AE），而安慰剂组没有。依匹木单抗组有 9 例（2%）患者因治疗相关 AE 死亡，安慰剂组无死亡病例。免疫相关 3-4 级 AE 分别发生在 31%和 2%的患者中。
依匹木单抗并未改善转移性去势抵抗性前列腺癌患者的总生存期。无进展生存期和前列腺特异性抗原反应率的提高表明该药在某些患者亚群中具有抗肿瘤活性。
