Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial.
Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial.
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对原发性肿瘤的放疗，用于新诊断的转移性前列腺癌（Stampede）：一项随机控制的3期试验。
DOI：
10.1016/s0140-6736(18)32486-3
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发表时间：
2018-12-01
期刊：
影响因子：
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通讯作者：
Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators
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作者：
Parker CC;James ND;Brawley CD;Clarke NW;Hoyle AP;Ali A;Ritchie AWS;Attard G;Chowdhury S;Cross W;Dearnaley DP;Gillessen S;Gilson C;Jones RJ;Langley RE;Malik ZI;Mason MD;Matheson D;Millman R;Russell JM;Thalmann GN;Amos CL;Alonzi R;Bahl A;Birtle A;Din O;Douis H;Eswar C;Gale J;Gannon MR;Jonnada S;Khaksar S;Lester JF;O'Sullivan JM;Parikh OA;Pedley ID;Pudney DM;Sheehan DJ;Srihari NN;Tran ATH;Parmar MKB;Sydes MR;Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators
基于以前的研究结果，我们假设前列腺放疗可以提高转移性前列腺癌患者的总生存率，并且在转移负荷低的患者中获益最大。我们的目的是比较转移性前列腺癌的治疗标准，有和没有放疗。我们在瑞士和英国的117家医院进行了一项随机对照的3期试验。符合条件的患者新诊断为转移性前列腺癌。我们将患者以1：1的比例随机分配至标准治疗组（对照组）或标准治疗加放疗组（放疗组）。按医院、随机化时的年龄、淋巴结受累、WHO体能状态、计划的雄激素剥夺治疗、计划的多西他赛使用（自2015年12月起）和常规阿司匹林或非甾体抗炎药使用对随机化进行分层。标准治疗为终身雄激素剥夺治疗，从2015年12月开始允许预先使用多西他赛。分配放疗的男性接受每日（55戈伊，分20次，持续4周）或每周（36戈伊，分6次，持续6周）方案，该方案在随机化前指定。主要结局是总生存期，以死亡人数衡量;该分析具有90%的把握度，单侧α为2.5%，风险比（HR）为0.75。次要结局是无失败生存期、无进展生存期、无转移性进展生存期、前列腺癌特异性生存期和症状性局部无事件生存期。分析使用考克斯比例风险和灵活的参数模型，调整分层因素。两个预先设定的亚组分析根据基线转移负荷和放疗计划检验前列腺放疗的效果。该试验已在ClinicalTrials.gov上注册，编号NCT 00268476。在2013年1月22日至2016年9月2日期间，2061名男性接受了随机分组，1029名被分配为对照组，1032名被分配为放疗组。分配的组是平衡的，中位年龄为68岁（IQR 63-73），前列腺特异性抗原的中位量为97 ng/mL（33-315）。367例（18%）患者接受了早期多西他赛治疗。1082例（52%）参与者在随机化前指定了每日放疗计划，979例（48%）参与者指定了每周放疗计划。819例（40%）男性转移负荷低，1120例（54%）转移负荷高，122例（6%）转移负荷未知。放疗可改善无失败生存率（HR 0.76，95%CI 0.68 - 0.84; p<0.0001），但不能改善总生存率（HR 0.92，95%CI 0.80 - 1.06; p= 0.266）。放疗耐受性良好，放疗期间报告了48例（5%）不良事件（放疗肿瘤组3-4级），放疗后报告了37例（4%）不良事件。在安全性人群中，各治疗组报告至少1起重度不良事件（不良事件通用术语标准3级或更严重）的比例相似（对照组398例[38%]，放疗组380例[39%]）。前列腺放射治疗并不能改善新诊断的转移性前列腺癌的复发性前列腺癌患者的总生存率。英国癌症研究、英国医学研究理事会、瑞士临床癌症研究集团、安斯泰来、克洛维斯肿瘤学、杨森、诺华、辉瑞和赛诺菲-安万特。
Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy. We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule. This trial is registered with ClinicalTrials.gov, number NCT00268476. Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63–73) and median amount of prostate-specific antigen of 97 ng/mL (33–315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival (HR 0·76, 95% CI 0·68–0·84; p<0·0001) but not overall survival (0·92, 0·80–1·06; p=0·266). Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3–4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 [38%] with control and 380 [39%] with radiotherapy). Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer. Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.