2014年12月3日讯 /生物谷BIOON/ --安斯泰来（Astellas）和Medivation合作研发的新一代前列腺癌口服药物Xtandi（enzalutamide）监管方面爆出大好消息。继今年9月FDA批准Xtandi用于前列腺癌化疗前治疗，近日欧盟也已批准Xtandi用于化疗前治疗。尽管强生（JNJ）新一代前列腺癌口服药物Zytiga早在2011年4月上市之后一直统治市场，但Xtandi具有单独用药的独特优势，业界预测，在欧美2大主要市场，Xtandi将颠覆Zytiga的霸主地位。
具体而言，欧盟已批准Xtandi用于雄激素剥夺疗法治疗失败但尚未接受化疗（即化疗初治）的无症状或轻微症状的转移性去势抵抗前列腺癌（mCRPC）成人患者的治疗。Xtandi的获批，是基于III期PREVAIL研究的总生存期（OS）积极数据。数据显示，与安慰剂相比，Xtandi使放射学恶化或死亡风险降低81%，使死亡风险降低29%，同时也显著延迟了首次化疗时间（28.0个月 vs 10.8个月）以及首次骨骼相关事件（SRE）的发生。今年9月，FDA批准Xtandi化疗前治疗适应症也是基于III期PREVAIL的积极数据。
分析师预计，鉴于这些结果以及化疗前治疗标签扩展，Xtandi的患者群体将显著扩张，Xtandi的临床用药时间将翻番，化疗前治疗的患者群体将翻3倍。Xtandi于2013年上市，比强生Zytiga晚了近一年半，但Xtandi有其独特优势，即可单独用药，而强生Zytiga需联合强的松（prednisone）用药。
强生Zytiga已收获的化疗前用药适应症，已助推该药在2014年上半年销售额达到10.7亿美元。然而，Xtandi自一上市便被临床医生快速采纳，作为前列腺癌化疗后治疗的首选药物。业界认为，鉴于Xtandi的单独用药优势及近期获批的化疗前适应症，该药有望颠覆Zytiga的霸主地位。
Xtandi（enzalutamide）是一种新颖的、每日一次的口服雄激素受体信号传导抑制剂，该药能够抑制雄激素受体信号传导通路中的多个步骤，旨在干扰睾酮结合前列腺癌细胞的能力，已被证明能够降低癌细胞的生长，并能诱导肿瘤细胞死亡。睾酮是一种男性激素，能够激化前列腺癌细胞的生长。
英文原文：XTANDI(enzalutamide) Now Approved in Europe for the Treatment of Men with Metastatic Castration-Resistant Prostate Cancer Who Are Chemotherapy-Naïve
Enzalutamide significantly reduced the risk of radiographic progression or death by 81% compared with placebo
Enzalutamide demonstrated a significant impact on overall survival compared to placebo
Men treated with enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared to placebo
Astellas Pharma Europe Ltd. today announced that the European Commission (EC) has granted a variation to amend the Marketing Authorisation for enzalutamide (trade name XTANDI™).1 Enzalutamide is now approved in Europe for the treatment of adult men with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.1
“Enzalutamide provides a viable treatment option for a broad population of men with mCRPC, regardless of age, or their readiness for chemotherapy, which provides a meaningful period of time during which men have their disease controlled without the need for chemotherapy”, said Professor Bertrand Tombal, MD, PhD, Chairman of the Division of Urology and Professor of Physiology, Université Catholique de Louvain (UCL) and European Principal Investigator for PREVAIL. “The decision from the European Commission to approve enzalutamide, an effective and well tolerated alternative to chemotherapy, is a very important milestone for men with prostate cancer that has advanced.”
The Marketing Authorisation approval is based on results from the pivotal phase III PREVAIL study which demonstrate that enzalutamide improves outcomes for men with advanced prostate cancer who have not received chemotherapy.2
Compared with placebo, enzalutamide reduced the risk of death by 29% (HR=0.71; p<0.001) and the risk of radiographic progression or death by 81% (HR=0.19; p<0.001). Men treated with enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared to placebo (28.0 months versus 10.8 months, respectively; HR=0.35; p<0.001).2
The most common clinically relevant adverse events among the enzalutamide population as compared with placebo-treated patients in the PREVAIL trial included fatigue, hot flush and hypertension. Hypertension was observed in 13% of enzalutamide versus 4% of placebo-treated patients. Grade 3 or higher cardiac adverse events were reported in 3% of enzalutamide versus 2% of placebo-treated patients. One patient (0.1%) out of the 871 patients treated with enzalutamide, and one patient (0.1%) out of 844 patients receiving placebo experienced a seizure.2
Enzalutamide was approved by the EC in June 2013 for the treatment of adult men with mCRPC whose disease has progressed on or after docetaxel therapy.3 The new indication makes enzalutamide available for men in whom chemotherapy is not yet clinically indicated. Astellas expects to launch enzalutamide in the chemotherapy-naïve setting in the first European countries, including the UK, from December 2014.