Cathomas Richard, Crabb Simon J, Mark Michael, Winterhalder Ralph, Rothermundt Christian, Elliott Tony, von Burg Philippe, Kenner Heike, Hayoz Stefanie, Vilei Simona Berardi, Rauch Daniel, Roggero Enrico, Mohaupt Markus G, Bernhard Jürg, Manetsch Gabriela, Gillessen Silke
Oncology/Hematology, Kantonsspital Graubünden, Chur, Switzerland.
Cancer Sciences Unit, University of Southampton, Southampton, United Kingdom.
Prostate. 2016 Dec;76(16):1519-1527. doi: 10.1002/pros.23236. Epub 2016 Jul 25.
We tested whether a switch maintenance treatment with orteronel, an oral inhibitor of androgen biosynthesis, prolongs disease control in men with metastatic castration-resistant prostate cancer (mCRPC) after documented disease stabilization with docetaxel.
Men with mCRPC and non-progressive disease after a cumulative dose of ≥300 mg/m docetaxel for first line treatment were randomized 1:1 to receive orteronel 300 mg twice daily or placebo. The primary endpoint was event-free survival (EFS) defined as the time from randomization to death or the combination of at least two of radiographic, clinical, or PSA progression. Ninety-six patients per arm were planned to demonstrate an improvement of median EFS from 4 months on placebo to 6.7 months on orteronel (hazard ratio (HR) 0.6; type I error 5% and power 90%).
Forty-seven patients (23 orteronel, 24 placebo) were randomized before premature closure of the trial because of discontinuation of clinical development of orteronel. Median EFS was 8.5 months with orteronel and 2.9 months with placebo (P = 0.001; HR 0.32; 95%CI 0.15-0.65). Median radiographic progression-free survival (rPFS) was 8.5 and 2.8 months (P = 0.02; HR 0.42; 95%CI 0.20-0.91) in the orteronel and placebo arm, respectively. PSA decline ≥50% was seen in 57% on orteronel and 4% on placebo. Toxicity was mainly mild, one patient on orteronel developed transient grade 3 adrenal insufficiency and one grade 4 pneumonitis.
Orteronel significantly prolongs EFS in men with mCRPC who achieve disease stabilization with docetaxel. The concept of switch maintenance therapy in mCRPC warrants further research. Prostate 76:1519-1527, 2016. © 2016 Wiley Periodicals, Inc.
我们测试了雄激素生物合成的口服抑制剂奥特雄酮进行的转换维持治疗，在多西他赛使疾病稳定后，是否能延长转移性去势抵抗性前列腺癌（mCRPC）男性患者的疾病控制时间。
一线治疗累积剂量≥300mg/m²多西他赛后疾病无进展的mCRPC男性患者按1:1随机分组，接受每日两次300mg奥特雄酮或安慰剂治疗。主要终点是无事件生存期（EFS），定义为从随机分组到死亡或影像学、临床或PSA进展中至少两项情况出现的时间。计划每组96例患者，以证明安慰剂组中位EFS为4个月，奥特雄酮组为6.7个月（风险比（HR）0.6；I型错误5%，检验效能90%）。
由于奥特雄酮临床研发的中断，47例患者（23例奥特雄酮组，24例安慰剂组）在试验提前结束前被随机分组。奥特雄酮组中位EFS为8.5个月，安慰剂组为2.9个月（P = 0.001；HR 0.32；95%CI 0.15 - 0.65）。奥特雄酮组和安慰剂组中位影像学无进展生存期（rPFS）分别为8.5个月和2.8个月（P = 0.02；HR 0.42；95%CI 0.20 - 0.91）。奥特雄酮组57%的患者PSA下降≥50%，安慰剂组为4%。毒性主要为轻度，1例接受奥特雄酮治疗的患者出现短暂的3级肾上腺功能不全，1例出现4级肺炎。
奥特雄酮可显著延长多西他赛使疾病稳定的mCRPC男性患者的EFS。mCRPC转换维持治疗的概念值得进一步研究。《前列腺》76:1519 - 1527，2016年。©2016威利期刊公司
