Cometriq获准用于某些甲状腺髓样癌患者

圣路易斯(MD Consult)——2012年11月29日，美国食品药品管理局(FDA)和Exelixis宣布，已批准Cometriq(cabozantinib)治疗进展性、转移性甲状腺髓样癌(MTC)。Cometriq是一种多重受体酪氨酸激酶抑制剂，在正常细胞功能和病理性过程(例如瘤形成、转移、肿瘤血管生成及肿瘤微环境的维持)中均发挥作用。

Cometriq的安全性和有效性在一项纳入330例进展性、转移性MTC患者的国际多中心随机双盲对照试验中得到了检验。入组患者被随机按2:1比例分组，每日1次口服Cometriq 140 mg(n=219)或安慰剂(n=111)，直至发生疾病进展(由负责的医生判断)或出现明显不能耐受的毒性。

与安慰剂组患者相比，Cometriq组患者的无进展生存期(PFS)显著延长，两组的中位PFS分别为4.0个月和11.2个月[危险比(HR)，0.28；95%置信区间(CI)，0.19~0.40；P＜0.0001]。仅在Cometriq组患者中观察到部分应答。Cometriq组患者的中位客观应答持续时间为14.7个月。按照计划进行的中期分析显示，两组在总生存率方面尚未出现显著差异。

研究受试者最常报告的药物不良反应为腹泻、口炎、手足综合征、体重下降、食欲减退、恶心、疲乏、口腔痛、发色改变、味觉障碍、高血压、腹痛和便秘。最常报告的实验室指标异常为肝酶水平升高、淋巴细胞减少、碱性磷酸酶水平升高、低钙血症、中性粒细胞减少、血小板减少、低磷血症和高胆红素血症。

Cometriq的处方信息包含一则加框警告，提醒患者和医务人员警惕潜在的严重甚至致死性胃肠道穿孔和瘘。此外，警示部分也包含了有关发生严重甚至致死性出血的可能性。

Cometriq的推荐剂量为140 mg口服1次/d(1粒80 mg胶囊和3粒20 mg胶囊)。Cometriq不得与食物同服，应告知患者在服用Cometriq之前至少2 h内和之后至少1 h内不要进食。

爱思唯尔版权所有  未经授权请勿转载

ST LOUIS (MD Consult) - On November 29, 2012, the US Food and Drug Administration and Exelixis announced the approval of Cometriq (cabozantinib) for the treatment of progressive, metastatic, medullary thyroid cancer (MTC). Cometriq is an inhibitor of multiple receptor tyrosine kinases involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.

Cometriq's safety and efficacy were assessed in an international, multicenter, randomized double-blind, controlled trial of 330 patients with progressive, metastatic MTC. Patients were randomly assigned (2:1) to receive either Cometriq 140 mg (n = 219) or placebo (n = 111) orally, once daily until disease progression occurred (as determined by the treating physician) or until intolerable toxicity became evident.

A statistically significant prolongation in progression-free survival (PFS) was demonstrated among Cometriq-treated patients compared with patients who received placebo (hazard rate 0.28 [95% confidence interval, 0.19-0.40]; P < .0001), with median PFS times of 11.2 months and 4.0 months in the Cometriq and placebo arms, respectively. Partial responses were observed only among patients in the Cometriq arm. The median duration of objective responses was 14.7 months for patients treated with Cometriq. No statistically significant difference in overall survival was apparent between the treatment arms at the planned interim analysis.

The most commonly reported adverse drug reactions in study participants were diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation. The most common laboratory abnormalities reported were increased liver enzyme levels, lymphopenia, increased alkaline phosphatase levels, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

The prescribing information for Cometriq includes a Boxed Warning alerting patients and health care professionals of the possibility that serious and sometimes fatal gastrointestinal perforations and fistulas may occur. In addition, the possibility of severe and sometimes fatal hemorrhage is also included in the warning.

The recommended dose of Cometriq is 140 mg orally, once daily (1 80-mg capsule and 3 20-mg capsules). Cometriq should not be taken with food, and patients should be advised to not eat for at least 2 hours before and at least 1 hour after taking Cometriq.