Olaratumab和阿霉素与阿霉素单独软组织肉瘤的治疗:非盲阶段1 b和随机第二阶段试验。

文章的细节

引用

复制到剪贴板

利用WD,琼斯RL,范齿英航,Chmielowski B,伊莱亚斯广告,Adkins D, Agulnik M, Cooney MM,利文斯顿MB, Pennock G, Hameed先生,沙GD,秦,Shahir,裙带DM, Ilaria小R,孔蒂,Cosaert J,施瓦茨星期

Olaratumab和阿霉素与阿霉素单独软组织肉瘤的治疗:非盲阶段1 b和随机第二阶段试验。

柳叶刀》。2016年7月30日,388 (10043):488 - 97。doi: 10.1016 / s0140 - 6736 (16) 30587 - 6。Epub 2016 6月9。

PubMed ID

27291997 (在PubMed

]

文摘

背景:与阿霉素治疗是目前转移性软组织肉瘤患者的护理标准和平均总生存期长达12 - 16个月的治疗,但很少,如果有的话,小说治疗或化疗组合能够改善这些可怜的结果。Olaratumab是人类antiplatelet-derived生长因子受体α单克隆抗体在人类肿瘤异种移植具有抗肿瘤活性。我们的目的是评估的有效性olaratumab +阿霉素在晚期或转移性软组织肉瘤患者。方法:我们做了一个非盲阶段1 b和随机的第二阶段研究阿霉素+ olaratumab治疗不可切除的患者或转移性软组织肉瘤临床网站在美国16岁。b阶段1和阶段2的部分研究,符合条件的患者18岁或以上,组织学证实诊断治疗的局部晚期或转移性软组织肉瘤不以前蒽环霉素,东部合作肿瘤组织(ECOG) 0 - 2的性能状态,通过免疫组织化学方法和可用的肿瘤组织确定PDGFRalpha表达式。在第二阶段的研究中,患者被随机分配在1:1的比例获得olaratumab(15毫克/公斤)静脉注射在每天1和8 +阿霉素(75毫克/米(2))或阿霉素单独(75毫克/米(2))的第1天每21天的周期8个周期。随机动态,运用最小化的随机方法。第一阶段b主要终点是安全,第二阶段主要终点是无进展生存使用双面α水平的0.2和0.8统计的力量。本研究在ClinicalTrials.gov注册,NCT01185964数量。发现:15个患者登记和处理olaratumab +阿霉素在阶段1 b的研究中,和133名患者被随机(66 olaratumab +阿霉素; 67 to doxorubicin alone) in the phase 2 trial, 129 (97%) of whom received at least one dose of study treatment (64 received olaratumab plus doxorubicin, 65 received doxorubicin). Median progression-free survival in phase 2 was 6.6 months (95% CI 4.1-8.3) with olaratumab plus doxorubicin and 4.1 months (2.8-5.4) with doxorubicin (stratified hazard ratio [HR] 0.67; 0.44-1.02, p=0.0615). Median overall survival was 26.5 months (20.9-31.7) with olaratumab plus doxorubicin and 14.7 months (9.2-17.1) with doxorubicin (stratified HR 0.46, 0.30-0.71, p=0.0003). The objective response rate was 18.2% (9.8-29.6) with olaratumab plus doxorubicin and 11.9% (5.3-22.2) with doxorubicin (p=0.3421). Steady state olaratumab serum concentrations were reached during cycle 3 with mean maximum and trough concentrations ranging from 419 mug/mL (geometric coefficient of variation in percentage [CV%] 26.2) to 487 mug/mL (CV% 33.0) and from 123 mug/mL (CV% 31.2) to 156 mug/mL (CV% 38.0), respectively. Adverse events that were more frequent with olaratumab plus doxorubicin versus doxorubicin alone included neutropenia (37 [58%] vs 23 [35%]), mucositis (34 [53%] vs 23 [35%]), nausea (47 [73%] vs 34 [52%]), vomiting (29 [45%] vs 12 [18%]), and diarrhoea (22 [34%] vs 15 [23%]). Febrile neutropenia of grade 3 or higher was similar in both groups (olaratumab plus doxorubicin: eight [13%] of 64 patients vs doxorubicin: nine [14%] of 65 patients). INTERPRETATION: This study of olaratumab with doxorubicin in patients with advanced soft-tissue sarcoma met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement of 11.8 months in median overall survival, suggesting a potential shift in the treatment of soft-tissue sarcoma. FUNDING: Eli Lilly and Company.

beplay体育安全吗DrugBank数据引用了这篇文章

药物

Olaratumab