《新英格蘭醫學雜誌》2017年6月4日在線先發

http://www.nejm.org/doi/full/10.1056/NEJMoa1704174#t=abstract

阿比特龍+強的松治療轉移性去勢敏感性前列腺癌

背景

醋酸阿比特龍是一種阻斷內源性雄激素合成的藥物，與強的松聯用可治療轉移性去勢抵抗性前列腺癌。在此，我們在新診斷出的轉移性去勢敏感性前列腺癌患者中，評價了阿比特龍+強的松聯合去勢治療的臨床獲益情況。

方法

在這項雙盲、安慰劑對照的3期臨床試驗中，我們隨機將1199名患者分組，接受去勢治療+阿比特龍（每日1000mg，250mg的片劑4片，每日一次）+強的松（每日5mg），或者接受去勢治療+雙安慰劑（安慰劑組）。兩個主要終點為總生存期和影像學評價的無進展生存期。

結果

在一次按計劃進行的中期分析時，中位隨訪30.4個月後，阿比特龍組中位總生存期明顯比安慰劑組長（中位總生存期未達到對比34.7個月）（死亡風險比，0.62；95%置信區間[CI]，0.51-0.76；P<0.001）。放射影像學評價的無進展生存期的中位時間，阿比特龍組為33.0個月，安慰劑組14.8個月（腫瘤進展或死亡風險比，0.47；95%CI，0.39-0.55；P<0.001）。我們觀察到阿比特龍組所有次要終點結果均明顯更佳，這些次要終點包括疼痛進展時間、前列腺癌下一步治療時間、開始化療時間、前列腺特異性抗原（PSA）進展時間（所有比較均P<0.001）以及下一個有癥狀的骨骼事件（P=0.009）。這些結果使得獨立數據和安全監管委員會一致推薦，本試驗應當揭盲，並允許將安慰劑組患者交叉到阿比特龍組。阿比特龍組3級高血壓和低血糖發生率較高。

結論

在新診斷出的轉移性去勢敏感性前列腺癌男性中，阿比特龍+強的松加入去勢治療明顯延長了總生存期和影像學評價的無進展生存期。

《壹篇》南南和北北

Abiraterone plus Prednisone in Metastatic,Castration-Sensitive Prostate Cancer

Karim Fizazi, M.D., Ph.D., NamPhuong Tran, M.D., Luis Fein,M.D., Nobuaki Matsubara, M.D., Alfredo Rodriguez-Antolin, M.D.,Ph.D., Boris Y. Alekseev, M.D., Mustafa Özgüroğlu, M.D., DingweiYe, M.D., Susan Feyerabend, M.D., Andrew Protheroe, M.D., Ph.D.,Peter De Porre, M.D., Thian Kheoh, Ph.D., Youn C. Park, Ph.D., MaryB. Todd, D.O., and Kim N. Chi, M.D., for the LATITUDEInvestigators*

June 4, 2017DOI: 10.1056/NEJMoa1704174

Background

Abiraterone acetate, a drug that blocks endogenous androgensynthesis, plus prednisone is indicated for metastaticcastration-resistant prostate cancer. We evaluated the clinicalbenefit of abiraterone acetate plus prednisone withandrogen-deprivation therapy in patients with newly diagnosed,metastatic, castration-sensitive prostate cancer.

Methods

In this double-blind, placebo-controlled, phase 3 trial, werandomly assigned 1199 patients to receive eitherandrogen-deprivation therapy plus abiraterone acetate (1000 mgdaily, given once daily as four 250-mg tablets) plus prednisone (5mg daily) (the abiraterone group) or androgen-deprivation therapyplus dual placebos (the placebo group). The two primary end pointswere overall survival and radiographic progression-freesurvival.

Results

After a median follow-up of 30.4 months at a planned interimanalysis (after 406 patients had died), the median overall survivalwas significantly longer in the abiraterone group than in theplacebo group (not reached vs. 34.7 months) (hazard ratio fordeath, 0.62; 95% confidence interval [CI], 0.51 to 0.76;P<0.001). The median length of radiographic progression-freesurvival was 33.0 months in the abiraterone group and 14.8 monthsin the placebo group (hazard ratio for disease progression ordeath, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantlybetter outcomes in all secondary end points were observed in theabiraterone group, including the time until pain progression, nextsubsequent therapy for prostate cancer, initiation of chemotherapy,and prostate-specific antigen progression (P<0.001 for allcomparisons), along with next symptomatic skeletal events(P=0.009). These findings led to the unanimous recommendation bythe independent data and safety monitoring committee that the trialbe unblinded and crossover be allowed for patients in the placebogroup to receive abiraterone. Rates of grade 3 hypertension andhypokalemia were higher in the abiraterone group.

Conclusions

The addition of abiraterone acetate and prednisone toandrogen-deprivation therapy significantly increased overallsurvival and radiographic progression-free survival in men withnewly diagnosed, metastatic, castration-sensitive prostate cancer.(Funded by Janssen Research and Development; LATITUDEClinicalTrials.gov number, NCT01715285.)

《壹篇》系主要面向醫務人員的公益性頭條號，不以營利為目的，不進行任何有償諮詢和服務，不出售任何產品，與ASCO、CSCO等所有專業學會和機構沒有任何關係和聯繫，也不代表任何官方學會發聲。

文章圖片均來自網路，不做商業用途，若有版權爭議請與《壹篇》聯繫。

堅持點贊、讚賞和轉發是一種態度和支持。