Kassem Loay, Shohdy Kyrillus S, Abdel-Rahman Omar
a Clinical Oncology Department, Kasr Alainy School of Medicine , Cairo University , Cairo , Egypt.
b Clinical Oncology Department, Faculty of Medicine , Ain Shams University , Cairo , Egypt.
Curr Med Res Opin. 2018 May;34(5):903-910. doi: 10.1080/03007995.2018.1447450. Epub 2018 Mar 27.
A major, yet precisely studied, shift has occurred in the treatment of advanced hormone-sensitive prostate cancer (HSPC) by the addition of docetaxel to androgen deprivation therapy (ADT) in the first line. Recently, two landmark trials showed that abiraterone acetate (AA) can be an effective alternative along with ADT in the same setting. We implemented a network meta-analysis to compare the safety and efficacy of the two combinations.
PubMed database, ASCO and ESMO meeting library databases of all results published until June 2017 were searched using the keywords: "prostate cancer" AND "docetaxel" OR "abiraterone acetate". Efficacy endpoints including progression-free survival (PFS) and overall survival (OS), and safety endpoints (including treatment related deaths and selected adverse events) were assessed.
Twenty relevant studies were retrieved and assessed for eligibility. Of those trials, eight were found potentially eligible. Inconsistent reporting of efficacy outcomes limited our analysis to M1 HSPC. The pooled hazard ratios (HRs) of OS and PFS of the direct comparison of abiraterone acetate plus ADT versus ADT were 0.63 (95% CI: 0.545-0.717) and 0.38 (95% CI: 0.34-0.43), respectively. Meanwhile, in the trials of docetaxel plus ADT the pooled HRs of OS and PFS were 0.75 (95% CI: 0.65-0.86) and 0.634 (95% CI: 0.57-0.70), respectively. The indirect comparison showed that the HRs of OS and PFS in DOC + ADT in comparison to AA + ADT were 1.2 (95% CI: 0.98-1.46) and 1.65 (1.40-1.94), respectively. The pooled RR of treatment-related mortality in docetaxel + ADT versus AA + ADT was 1.438 (95% CI: 0.508-4.075).
Patients with metastatic HSPC (mHSPC) who received abiraterone acetate with ADT had better PFS and less toxicity compared to those receiving docetaxel with ADT. A trend towards superior OS and fewer treatment-related deaths was also observed, but was statistically non-significant. In view of lacking clear OS advantage, the choice between docetaxel and AA should include a discussion with the patient about the potential toxicities and impact on quality of life of each regimen.
在一线雄激素剥夺治疗（ADT）中加入多西他赛后，晚期激素敏感性前列腺癌（HSPC）的治疗发生了重大但尚未得到精确研究的转变。最近，两项具有里程碑意义的试验表明，醋酸阿比特龙（AA）在相同情况下可作为ADT的有效替代方案。我们进行了一项网状Meta分析，以比较这两种联合治疗的安全性和疗效。
使用关键词“前列腺癌”和“多西他赛”或“醋酸阿比特龙”检索截至2017年6月发表的所有结果的PubMed数据库、美国临床肿瘤学会（ASCO）和欧洲肿瘤内科学会（ESMO）会议文库数据库。评估了包括无进展生存期（PFS）和总生存期（OS）在内的疗效终点以及安全性终点（包括治疗相关死亡和选定的不良事件）。
检索到20项相关研究并评估其是否符合纳入标准。在这些试验中，发现8项可能符合条件。疗效结果报告不一致，限制了我们仅对M1期HSPC进行分析。醋酸阿比特龙联合ADT与ADT直接比较的OS和PFS合并风险比（HR）分别为0.63（95%CI：0.545 - 0.717）和0.38（95%CI：0.34 - 0.43）。同时，在多西他赛联合ADT的试验中，OS和PFS的合并HR分别为0.75（95%CI：0.65 - 0.86）和0.634（95%CI：0.57 - 0.70）。间接比较显示，与AA联合ADT相比，多西他赛联合ADT的OS和PFS的HR分别为1.2（95%CI：0.98 - 1.46）和1.65（1.40 - 1.94）。多西他赛联合ADT与AA联合ADT治疗相关死亡率的合并相对危险度（RR）为1.438（95%CI：0.508 - 4.075）。
与接受多西他赛联合ADT的转移性HSPC（mHSPC）患者相比，接受醋酸阿比特龙联合ADT的患者具有更好的PFS且毒性更低。还观察到OS有优势且治疗相关死亡较少的趋势，但在统计学上无显著意义。鉴于缺乏明确的OS优势，在多西他赛和AA之间的选择应包括与患者讨论每种治疗方案的潜在毒性及其对生活质量的影响。
