在LATITUDE研究的中期分析中，醋酸阿比特龙（abiraterone acetate ）联合强的松雄激素剥夺疗法(ADT)与安慰剂加ADT相比，新诊断的高危转移性去雄敏感前列腺癌(mCSPC)患者的总体生存率和影像学无进展生存率有显着改善。刚发表于《Lancet oncology》的临床研究文章中，研究者从LATITUDE研究的最终分析中提出了abiraterone acetate加强的松和ADT的长期生存结果和安全性。

　　这是一项多中心、随机、双盲III期临床试验，在34个国家的235个机构开展。符合条件的新诊断患者(年龄≥18岁男性)经病理或细胞学上证实前列腺癌转移。患者东部合作肿瘤组(ECOG)状态 0 - 2,并且至少两三个高风险预后因素(Gleason评分≥8，骨扫描存在三个或三个以上病变,或存在的可衡量的内脏转移，但淋巴结转移除外)。将患者随机分组(1:1)，每日口服阿比特龙(1000 mg) +强的松(5 mg)一次，每日口服ADT(阿比特龙+强的松组)或安慰剂+ ADT(安慰剂组);每个治疗周期为28天。
　　
　　在2013年2月12日至2014年12月11日期间，共筛查1209例患者，其中10例因研究场地违规而不符合入选条件。1199例患者随机分为醋酸阿比特龙加强的松组(n=597)和安慰剂组(n=602)。最终分析时(数据截止于2018年8月15日)，中位随访51·8个月(IQR 47·2-57·0)，发现618例死亡(醋酸阿比特龙加强的松组597例，275例[46%]死亡，安慰剂组602例，343例[57%])。醋酸阿比特龙联合强的松组总生存期(中位53·3个月[95% CI 48·2 -])明显长于安慰剂组(36·5个月[33·5 - 40·0])，危险比为0·66 (95% CI 0·56-0·78);p < 0·0001)。
　　
　　最常见的3 - 4级不良事件是高血压(醋酸阿比特龙+强的松组125人(21%)、安慰剂组60人(10%)组和在72名从安慰剂组交叉到醋酸阿比特龙+强的松中的3名(4%))和低钾血症(70名(12%)、10名(2%)和两名[3%])。在597例患者中，醋酸阿比特龙加强的松组192例(32%)发生严重不良反应，安慰剂组151例(25%)发生严重不良反应，交叉组72例(6%)发生严重不良反应。最常见的与治疗相关的严重不良事件是低钾血症(醋酸阿比特龙加强的松组有4例[1%]患者，其他组无一例)。醋酸阿比特龙联合强的松组(胃溃疡穿孔、猝死、脑血管意外)和安慰剂组(猝死、脑血管意外、肺炎)治疗相关死亡各3例(<1%)，交叉组无一例。
　　
　　该研究认为，在新近诊断为高危mCSPC的男性患者中，阿比特龙醋酸盐联合强的松联合ADT与安慰剂联合ADT相比，总体生存期显着延长，且安全性可控。这些结果支持使用醋酸阿比特龙加强的松作为高危mCSPC患者的治疗标准。
　　
　　原文摘要：
　　
　　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 0–2, 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 47·2–57·0) 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–not reached]) than in the placebo group (36·5 months [33·5–40·0]), with a hazard ratio of 0·66 (95% CI 0·56–0·78; p<0·0001). The most common grade 3–4 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.
　　
　　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
　　
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