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今年9月，FDA批准安斯泰来（Astellas）前列腺癌口服药物Xtandi（enzalutamide）扩大适应症，用于前列腺癌化疗前治疗，此前业界预测，在美国市场，Xtandi将颠覆强生Zytiga霸主地位。近日，Xtandi在欧盟监管方面也收获了好消息。欧洲药品管理局（EMA）人用医药产品委员会（CHMP）也建议批准Xtandi用于前列腺癌化疗前治疗。欧盟委员会（EC）在审批药物时通常都会采纳CHMP的建议。这也意味着，继美国市场，未来几个月，Xtandi也将在欧洲市场挑战Zytiga的霸主地位。
强生（JNJ）新一代前列腺癌口服药物Zytiga于2011年4月上市之后一直统治市场。FDA于2012年12月批准Zytiga用于前列腺癌化疗前治疗，进一步扩大了治疗群体，并为强生带来了滚滚财源，该药2013年的销售额为17亿美元，2014年仅上半年就达到10.5亿美元。
安斯泰来Xtandi于2012年8月在美国上市，尽管上市时间比Zytiga晚了近一年半，但强生Zytiga需联合强的松（prednisone）用药，而Xtandi具有单独用药的独特优势，因此，自一上市Xtandi就赢得了临床医生和患者的青睐，作为前列腺癌化疗后治疗的首选药物，对强生Zytiga形成了严峻挑战。另外，Xtandi于今年9月获FD批准用于前列腺癌化疗前治疗，剑锋更是直指Zytiga。
近日，在欧盟，CHMP已建议批准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。CHMP的积极意见是基于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%（HR=0.19，p＜0.001），使死亡风险降低29%（HR=0.71，p＜0.001），同时也显著延迟了首次化疗时间（28.0个月 vs 10.8个月，HR=0.35，p＜0.0001）以及首次骨骼相关事件（SRE）的发生。此前，FDA批准Xtandi化疗前治疗适应症也是基于III期PREVAIL的积极数据。
有分析师预计，鉴于这些结果以及药物标签的扩展，Xtandi的患者群体将显著扩张，化疗前治疗适应症将使Xtandi的临床用药时间翻番，化疗前治疗的患者群体将翻3倍。业界预测，基于Xtandi单独用药的独特优势及化疗前治疗适应症，在美欧两大市场，Xtandi有望颠覆强生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) CAPSULES RECEIVE POSITIVE CHMP OPINION FOR THE TREATMENT OF MEN WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO ARE CHEMOTHERAPY-NA?VE
For chemotherapy-na?ve patients, enzalutamide demonstrated a significant impact on overall survival compared to placebo
Enzalutamide reduced the risk of death by 29% versus placebo
Enzalutamide significantly reduced the risk of radiographic progression or death by 81% compared with placebo
Patients experienced delayed time to initiation of chemotherapy with enzalutamide compared with those taking placebo
Astellas Pharma Europe Ltd. today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending a variation to amend the Marketing Authorisation for enzalutamide (trade name XTANDI?). The positive opinion relates to the use of enzalutamide for the treatment of adult men with metastatic castrate-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
“For us urologists treating patients with mCRPC, this positive opinion from the CHMP is an important milestone towards making enzalutamide available across Europe. Enzalutamide marks a significant step for many patients who live with mCRPC as encouraging, it demonstrates benefits in overall survival, has a positive impact on quality of life and has been shown to be well tolerated”, said Professor Bertrand Tombal, MD, PhD, Chairman of the Division of the Urology and Professor of Physiology, Université Catholique de Louvain (UCL) and European Principal Investigator for PREVAIL. “As well as clear efficacy and safety benefits over placebo, enzalutamide has the additional advantage of not requiring steroids to be taken concomitantly and requires only basic monitoring, making it a simple option for both healthcare professionals and patients. It is my hope that the European Commission follows this opinion, providing us with a viable new treatment option for those patients not suitable for chemotherapy.”
The positive CHMP opinion is based on results from the phase III PREVAIL study which showed that men treated with enzalutamide demonstrated a statistically significant reduction both in the risk of death and a delay in cancer progression and the time to initiation of chemotherapy as compared to those treated with placebo.2
Enzalutamide reduced the risk of death by 29% (HR=0.71; p<0.001), compared with placebo. In addition, treatment with enzalutamide significantly reduced the risk of radiographic progression or death by 81% compared with placebo treatment (HR=0.19; p<0.001). Men taking enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared with men taking placebo (28.0 months versus 10.8 months; HR=0.35; p<0.0001).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%) receiving placebo experienced a seizure.2
In the EU, the European Commission generally follows the recommendations of the CHMP opinion and delivers its final decision around two months after the CHMP recommendation.
XTANDI is currently licensed in Europe for the treatment of adult men with mCRPC whose disease has progressed on or after docetaxel therapy.3 Marketing authorisation was granted by the European Commission in June 2013.