ST LOUIS (MD Consult) - On November 18, 2010, Amgen announced that the US Food and Drug Adminstration (FDA) has approved Xgeva (denosumab) for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. Xgeva is a fully human monoclonal antibody that binds to RANK ligand, a protein essential for the formation, function, and survival of osteoclasts. It is believed that Xgeva works by preventing RANK ligand from activating its receptor (RANK) on the surface of osteoclasts, thereby decreasing bone destruction.

The FDA approval of Xgeva was granted on the basis of results from 3 pivotal, phase 3, head-to-head trials that evaluated the use of Xgeva delivered every 4 weeks as a 120-mg subcutaneous injection versus the use of Zometa (zoledronic acid) delivered every 4 weeks via a 15-minute intravenous infusion. In the phase 3 trials, patients given Xgeva demonstrated a clinically meaningful improvement in preventing SREs compared with patients given Zometa. Specifically, in patients with breast or prostate cancer and bone metastases, Xgeva was superior to Zometa in reducing the risk of SREs. In patients with bone metastasis associated with other solid tumors or bone lesions from multiple myeloma, Xgeva was noninferior (trending towards superiority) to Zometa in reducing the risk of SREs. Superiority was also seen in the integrated analysis of the phase 3 studies, according to Amgen.

The most common adverse reactions in patients receiving Xgeva were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction in patients receiving Xgeva was dyspnea. The most common adverse reactions resulting in discontinuation of Xgeva were osteonecrosis and hypocalcemia.

Overall rates of adverse events and serious adverse events were generally similar between patients given Xgeva or Zometa. Osteonecrosis of the jaw was infrequent, with no statistically significant difference between treatment arms. Hypocalcemia occurred more frequently in patients in the Xgeva arm. Overall survival and progression-free survival were similar between arms in all 3 trials.

圣路易斯(MD Consult)——2010年11月18日，美国安进公司宣布，美国食品药品管理局(FDA)已经批准Xgeva(狄诺塞麦)用于预防实体瘤骨转移患者的骨骼相关事件(SRE)。Xgeva是一种与核因子-κB受体活化因子(RANK)配体结合的完全人源化单克隆抗体，RANK配体是破骨细胞形成、功能调节和生存不可缺少的一种蛋白质。Xgeva被认为是通过阻止RANK配体激活破骨细胞表面的受体(RANK)发挥作用的，从而减少骨破坏。

FDA批准Xgeva是基于3项关键性的III期直接比较试验的结果，这些试验对每4周皮下注射Xgeva 120 mg与每4周静脉注射择泰(唑来膦酸)持续15 min进行了评估。这些III期试验证实，与择泰治疗组患者相比，Xgeva治疗组患者在SRE的预防方面具有临床意义的改善。详言之，对于乳腺癌或前列腺癌骨转移患者来说，Xgeva在降低SRE风险方面的疗效优于择泰。对于其他实体瘤骨转移或多发性骨髓瘤骨病变的患者而言，Xgeva在降低SRE风险方面的疗效并不劣于(有较优的趋势)择泰。据安进公司称，在对III期研究进行的综合分析中也观察到了这种优势。

使用Xgeva的患者发生的最常见的不良反应是疲乏/无力、低磷血症和恶心。使用Xgeva的患者发生的最常见的严重不良反应是呼吸困难。导致Xgeva停用的最常见的不良反应是骨坏死和低钙血症。

在使用Xgeva或择泰的患者中不良事件和严重不良事件的总发生率基本上相近。两个治疗组的患者较少发生下颌骨坏死，亦无显著的组间差异。Xgeva治疗组中低钙血症的发生率较高。在这3项试验中，两治疗组间的总生存和无进展生存均相近。