Xgeva获准用于治疗某些巨型骨细胞瘤患者

圣路易斯(MD Consult)——2013年6月13日，美国食品药品管理局(FDA)宣布Xgeva(狄诺塞麦)用于治疗无法手术切除或手术切除可能导致严重合并症的成年及骨骼发育成熟的青少年巨型骨细胞瘤患者。狄诺塞麦治疗巨型骨细胞瘤的推荐剂量和疗程安排为120 mg、每4周1次皮下注射，在第1个月的第8天和第15天另外追加120 mg的剂量。

FDA批准狄诺塞麦是基于2项多中心开放标签试验的观察结果。据观察，在这些试验中狄诺塞麦可产生持久的客观应答；其受试者为成人及骨骼成熟的青少年巨型骨细胞瘤患者，其病情经过组织学确诊且肿瘤大小可测。这些肿瘤要么是复发的、不可切除的，要么是肿瘤处于拟行手术很可能会导致严重合并症的部位。这些患者接受的治疗方案为120 mg狄诺塞麦，每4周1次，在第1个月的第8天和第15天另外追加剂量。总共有304例患者接受了狄诺塞麦治疗，其中位年龄为33岁(范围：13~83岁)，总共有10例患者是骨骼成熟的青少年(年龄介于13~17岁)。有187例(61%)患者在基线时及狄诺塞麦治疗后接受了放射学评估并有资料可查。

在187例患者中有47例出现客观应答，总应答率为25%。所有的应答均为部分应答。距出现应答的估计中位时间为3个月。这47例出现客观应答的患者的中位随访时间为20个月，51%的患者(24例/47例)客观应答的持续时间≥8个月。3例患者在出现客观应答后病情进展。

研究者对304例接受了至少1剂狄诺塞麦的骨巨细胞瘤患者进行了安全性数据分析。在这些患者中，有145例接受了至少1年治疗。最常见的不良反应为关节痛、头痛、恶心、背痛、疲乏及四肢痛。最常见的严重不良反应为下颌骨坏死和骨髓炎。

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ST LOUIS (MD Consult) - On June 13, 2013, the US Food and Drug Administration (FDA) announced the approval of Xgeva (denosumab) for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. The recommended dose and schedule of denosumab for the treatment of giant cell tumor of bone is 120 mg administered subcutaneously (subq) every 4 weeks with additional 120-mg doses on days 8 and 15 of the first month.

Denosumab's approval was granted on the basis of the demonstration of durable objective responses observed in 2 multicenter open-label trials that enrolled adults and skeletally mature adolescents with histologically confirmed, measurable giant cell tumor of bone. These tumors were either recurrent, unresectable, or were located where planned surgery was likely to result in severe morbidity. Patients received 120 mg denosumab subq every 4 weeks with additional doses on days 8 and 15 of the first month. A total of 304 patients received denosumab. The median age was 33 years (range, 13-83 years), and a total of 10 patients were skeletally mature adolescents (aged 13-17 years). Radiographic assessments at baseline and after denosumab treatment were available for 187 (61%) patients.

An objective response was identified in 47 of 187 patients for an overall response rate of 25%. All responses were partial responses. The estimated median time to response was 3 months. In the 47 patients with an objective response, the median duration of follow-up was 20 months, and 51% (24/47) experienced responses of at least 8 months duration. Three patients experienced disease progression after an objective response.

Safety data were evaluated in 304 patients with giant cell tumor of bone who received at least one dose of denosumab. Of these patients, 145 were treated for at least 1 year. The most common adverse reactions were arthralgia, headache, nausea, back pain, fatigue, and pain in the extremity. The most common serious adverse reactions were osteonecrosis of the jaw and osteomyelitis.