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[ASCO2015]早期化疗延长晚期前列腺癌生存期?

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第51届美国临床肿瘤学会(ASCO)年会将于5月29日-6月2日在芝加哥召开。13日,ASCO发表了四项重要研究,分别为广泛使用维生素片可减少非黑色素瘤皮肤癌风险,早期化疗可延长晚期前列腺癌患者生命,以及可以提高罕见肾癌儿童和复发性多发性骨髓瘤成人预后的新治疗方案。 整理如下:


多西他赛和/或唑来膦酸治疗激素缺乏的前列腺癌:来自STAMPEDE研究的第一个总生存期结果(摘要5001)


背景:STAMPEDE是一项应用新型多组多阶段设计的随机对照试验。本试验入组了高危局限性晚期或转移性前列腺癌(PCa)男性患者(pts),这些患者第一次开始长期内分泌治疗(HT)。该试验起初评估了加入3种治疗方法中的1种或2种到标准疗法中(SOC)。研究人员对比了3项研究的原始生存结果,这3项研究通过所有的中间分析[多西他赛(D)、唑来膦酸(ZA),和(D)+(ZA)组合]招募受试者。


方法:SOC是激素治疗≥3年;直到2011年11月份,鼓励N0M0患者行RT,然后再强制;RT是N+M0患者的可选方案。按照2:1:1:1的比例随机分层分配患者:SOC(对照),SOC+D,SOC+ZA,和SOC+D+ZA。ZA每次4mg,每三周一次,共6个周期,然后,每四周一次,直到2年。D每次75mg/m2,每三周一次,共6个周期,同时每天给予10mg氢化波尼松。


主要终点指标是生存期(从随机入组到由任何原因引起死亡的时间)。两两比较每组患者的生存期,90%的P值为单侧α2.5%,风险比0.75,要求对照组出现~400例死亡病例,包括对无复发生存期分析的3对中间缺益分析。分析采用对数秩检验的Cox模型,根据分层因素进行调整。


结果:从2005年10月到2013年3月,2962例患者随机入组到这四个组中。患者中位年龄是65岁;61%的转移癌,14%的N+/XM0,22%的N0M0;93%的患者在确诊后6个月内随机入组,中位PSA为65ng/ml。中位随访时间42个月。


在SOC、SOC+D、SOC+ZA和SOC+D+ZA组中3~5级毒性反应发生率分别为31%(SOC),50%(SOC+D)、32%(SOC+ZA)和52%(SOC+D+ZA)。对照组有405例死亡(84%死于PCa)。SOC+D vs SOC、SOC+ZA vs SOC、SOC+D+ZA vs SOC的风险比分别为0.76(95% CI 0.63,0.91;P=0.003)、0.93(95% CI 0.79,1.11;P=0.437)、0.81(95% CI 0.68,0.97;P=0.020)。SOC和SOC+D组的中位生存期分别为67个月和77个月,提高了10个月。M0和M1期的研究结果不久会提交。


结论:来自STAMPEDE试验的生存数据显示,对于初次开始长期接受内分泌治疗的男性患者,在治疗时加入多西他赛而不是唑来膦酸可以获得临床和统计学的显著生存改善。


摘要原文:


Background: STAMPEDE is a randomised controlled trial using a novel multi-arm multi-stage design. It recruits men (pts) with high-risk locally advanced or metastatic prostate cancer (PCa) starting long-term hormone therapy (HT) for the first time. The trial initially assessed adding 1 or 2 of 3 treatment approaches to standard of care (SOC). We report primary survival results for 3 research comparisons that recruited through all their intermediate analyses: docetaxel (D), zoledronic acid (ZA) & the combination (D+ZA). 


Methods: SOC was hormone therapy for > = 3yrs; RT was encouraged for N0M0 pts up to Nov-2011, then mandated; RT was optional for N+M0 pts. Stratified randomisation allocated pts 2:1:1:1 to SOC (control), SOC+D, SOC+ZA or SOC+D+ZA. 4mg ZA was given for six 3-weekly cycles then 4-weekly until 2yrs. D was given as 75mg/m2 for six 3-weekly cycles with prednisolone 10mg daily. The primary outcome measure was survival (time from randomisation to death from any cause). Pairwise comparisons to control on survival for each research arm had 90% power at 2.5% 1-sided alpha for a hazard ratio of 0.75 requiring ~400 control arm deaths, accounting for 3 intermediate lack-of-benefit analyses on failure-free survival. Analyses used the Cox model of the logrank test, adjusted for stratification factors. 


Results: From Oct-2005 to Mar-2013, 2,962 pts were randomised to the 4 arms. The groups were balanced with median age 65yrs; 61% metastatic, 14% N+/XM0, 22% N0M0; 93% diagnosed within 6m of randomisation; median PSA 65ng/ml. Median follow-up was 42m. Grade 3-5 toxicity was reported for 31% SOC, 50% SOC+D, 32% SOC+ZA and 52% SOC+D+ZA.There were 405 deaths on the control arm (84% from PCa). The hazard ratio was 0.76 (95% CI 0.63, 0.91; p = 0.003) for SOC+D vs SOC; 0.93 (95% CI 0.79, 1.11; p = 0.437) for SOC+ZA vs SOC; and 0.81 (95% CI 0.68, 0.97; p = 0.020) for SOC+D+ZA vs SOC. Median survival was increased by 10m from 67m on SOC to 77m on SOC+D. Results in M0 and M1 disease will be shown. 


Conclusions: Survival data from STAMPEDE show a clinically and statistically significant improvement in survival from adding docetaxel but not from adding zoledronic acid in men starting long-term hormone therapy for the first time.


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