在LATITUDE科学研究的中后期剖析中，醋酸阿比特龙（abiraterone acetate ）协同强的松雄性激素夺走治疗法(ADT)与安慰剂加ADT对比，新确诊的高风险肿瘤转移去雄比较敏感前列腺肿瘤(mCSPC)患者的整体存活率和影像诊断无进度存活率有显着改进。刚发布于《Lancet oncology》的临床实验文章内容中，学者从LATITUDE科学研究的最后剖析中明确提出了abiraterone acetate加强的松和ADT的长期性存活結果和安全系数。
它是一项多管理中心、任意、双盲实验III期临床研究，在34个我国的235个组织进行。满足条件的新确诊患者(年纪≥18岁男士)经病理学或细胞学上确认前列腺肿瘤迁移。患者东部地区协作恶性肿瘤组(ECOG)情况 0 – 2,而且最少两三个高危愈后要素(Gleason得分≥8，骨扫描存有三个或三个之上变病,或存有的可考量的内脏器官迁移，但淋巴结转移以外)。将患者随机分组(1:1)，每日内服阿比特龙(1000 mg) 强的松(5 mg)一次，每日内服ADT(阿比特龙 强的松组)或安慰剂 ADT(安慰剂组);每一个医治周期时间为28天。
在2013年2月12日至2014年12月11日期内，共筛选1209例患者，在其中10例因科学研究场所违反规定而不符当选标准。1199例患者任意分成醋酸
阿比特龙加强的松组(n=597)和安慰剂组(n=602)。最后剖析时(数据信息截至于2018年8月15日)，中位随诊51・8个月(IQR 47・2-57・0)，发觉618例身亡(醋酸阿比特龙加强的松组597例，275例[46%]身亡，安慰剂组602例，343例[57%])。醋酸阿比特龙协同强的松组总存活期(中位53・3个月[95% CI 48・2 -])显著善于安慰剂组(36・5个月[33・5 – 40・0])，风险之比0・66 (95% CI 0・56-0・78);p < 0・0001)。
最普遍的3 – 四级不良反应是血压高(醋酸
阿比特龙 强的松组125人(21%)、安慰剂组60人(10%)组与在72名从安慰剂组交叉式到醋酸阿比特龙 强的松中的3名(4%))和低血钾(70名(12%)、10名(2%)和两位[3%])。在597例患者中，醋酸阿比特龙加强的松组192例(32%)产生比较严重副作用，安慰剂组151例(25%)产生比较严重副作用，交叉式组72例(6%)产生比较严重副作用。最普遍的与医治有关的比较严重不良反应是低血钾(醋酸阿比特龙加强的松组是4例[1%]患者，别的组无一例)。醋酸阿比特龙协同强的松组(胃炎破孔、卒死、脑颅损伤意外)和安慰剂组(卒死、脑颅损伤意外、肺部感染)医治有关身亡各3例(<1%)，交叉式组无一例。
该科学研究觉得，在新近确诊为高风险mCSPC的男士患者中，
阿比特龙醋酸盐协同强的松协同ADT与安慰剂协同ADT对比，整体存活期显着增加，且安全系数可控性。这种結果适用应用醋酸阿比特龙加强的松做为高风险mCSPC患者的医治规范。
全文引言：
Background
In the interim analyses of the LATITUDE study, the addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) led to a significant improvement in overall survival and radiographic progression-free survival compared with placebos plus ADT in men with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (mCSPC). Here, we present long-term survival outcomes and safety of abiraterone acetate plus prednisone and ADT from the final analysis of the LATITUDE study.
Methods
This is a multicentre, randomised, double-blind, phase 3 trial done at 235 sites in 34 countries. Eligible patients (men aged ≥18 years) had newly diagnosed, histologically or cytologically confirmed prostate cancer with metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 0�C2, and at least two of the three high-risk prognostic factors (Gleason score of ≥8, presence of three or more lesions on bone scan, or presence of measurable visceral metastasis except lymph node metastasis). Patients were randomly assigned (1:1) to receive abiraterone acetate (1000 mg) once daily orally plus prednisone (5 mg) once daily orally and ADT (abiraterone acetate plus prednisone group) or matching placebos plus ADT (placebo group); each treatment cycle was 28 days. Randomisation was done by a centralised interactive web response system in a country-by-country scheme using permuted block randomisation, stratified by presence of visceral disease and ECOGperformance status. The coprimary endpoint of overall survival was assessed in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT01715285 and is complete.
Findings
Between Feb 12, 2013, and Dec 11, 2014, 1209 patients were screened, of whom ten were ineligible because of study site violations. 1199 patients were randomly assigned to either the abiraterone acetate plus prednisone group (n=597) or placebo group (n=602). After the results of the first interim analysis (cutoff date Oct 31, 2016), the study was unmasked to patients and investigators, and patients in the placebo group were allowed to cross over to receive abiraterone acetate and prednisone plus ADT treatment as per a protocol amendment (Feb 15, 2017) in an open-label extension phase of the study (up to 18 months from the protocol amendment). This final analysis (data cutoff Aug 15, 2018) was done after a median follow-up of 51・8 months (IQR 47・2�C57・0) and 618 deaths (275 [46%] of 597 in the abiraterone acetate plus prednisone group and 343 [57%] of 602 in the placebo group). Overall survival was significantly longer in the abiraterone acetate plus prednisone group (median 53・3 months [95% CI 48・2�Cnot reached]) than in the placebo group (36・5 months [33・5�C40・0]), with a hazard ratio of 0・66 (95% CI 0・56�C0・78; p<0・0001). The most common grade 3�C4 adverse events were hypertension (125 [21%] in the abiraterone acetate plus prednisone group vs 60 [10%] in the placebo group vs three [4%] in the 72 patients who crossed over from placebo to abiraterone acetate plus prednisone) and hypokalaemia (70 [12%] vs ten [2%] vs two [3%]). Serious adverse events of any grade occurred in 192 (32%) of 597 patients in the abiraterone acetate plus prednisone group, 151 (25%) of 602 in the placebo group, and four (6%) of 72 in the crossover group. The most common treatment-related serious adverse event was hypokalaemia (four [1%] patients in the abiraterone acetate plus prednisone group and none in the other groups). Treatment-related deaths occurred in three (<1%) patients each in the abiraterone acetate plus prednisone group (gastric ulcer perforation, sudden death, and cerebrovascular accident) and the placebo group (sudden death, cerebrovascular accident, and pneumonia), with none in the crossover group.
Interpretation
The combination of abiraterone acetate plus prednisone with ADT was associated with significantly longer overall survival than placebos plus ADT in men with newly diagnosed high-risk mCSPC and had a manageable safety profile. These findings support the use of abiraterone acetate plus prednisone as a standard of care in patients with high-risk mCSPC.
论文参考文献：
KarimFizazi et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet oncology, 12 April 2019
