2016年7月22日，欧盟人用药品委员会（CHMP）推荐批准了两款治疗晚期肾细胞癌的药物，分别是Ispen公司的Cabometyx (卡博替尼) 和卫材公司的 Kisplyx (lenvatinib) ，适用于既往接受过抗VEGF疗法的晚期肾细胞癌患者。
Cabometyx作为单药疗法使用，Kisplyx需与依维莫斯联用。Cabometyx和Kisplyx之前均已在EMA获批用于治理甲状腺癌。
肾细胞癌是最常见的成人肾癌类型。全球大约有33.8万例肾癌患者，其中美国约有5.8万例，欧洲约11.5万例，日本约1.7万例。肾细胞癌在所有肾癌患者中的比例超过90%，男性发病率一般是女性的2倍。晚期或转移性肾细胞癌患者通常难以进行手术治疗，标准疗法一般为分子靶向药物，但5年生存率仅有12.1%。尽管近期批准了一些肾细胞癌新药，但仍有很多患者对现有疗法响应不足，预后较差，亟需新的治疗选择。
由于肾细胞癌是一类医疗需求远未得到满足的疾病，Cabometyx和Kisplyx此次均以加速审评方式获得EMA批准。
CHMP推荐批准Cabometyx主要基于一项纳入658例接受VEGFR抑制剂治疗后疾病进展的转移性肾细胞患者的III期研究的结果。Cabometyx治疗组的PFS相比依维莫斯治疗组得到了延长（7.4 vs 3.8个月），初步结果显示总生存期也得到延长（21.4 vs 16.5个月）。
Cabometyx最常见的不良反应包括腹泻、疲乏、恶心、食欲不振、高血压、呕吐等。CHMP认为Cabometyx的风险获益在可接受的范围内。
CHMP推荐批准Kisplyx主要基于一项纳入153例接受过至少1种抗VEGF疗法的转移性或不可手术切除晚期肾细胞癌患者的Ib/II期研究的结果。Kisplyx+依维莫斯治疗组相比单独使用依维莫斯治疗组的PFS延长7.2个月（12.8 vs 5.6个月），而且已显示出总生存期延长的信号。最常见不良反应包括腹泻、疲乏、食欲不振、呕吐、恶心和高血压，其中严重腹泻的发生率高于依维莫斯单独用药组。CHMP认为Kisplyx+依维莫斯的治疗获益大于风险，但要求开展上市后研究来收集进一步的安全性和疗效数据。
EMA Recommends Granting a Marketing Authorisation for Lenvatinib in the Treatment of Unresectable Advanced or Metastatic RCC
Lenvatinib is indicated in combination with everolimus following one prior VEGF-targeted therapy
On 21 July 2016, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending granting a marketing authorisation for the medicinal product lenvatinib (Kisplyx), intended for the treatment of patients with unresectable advanced or metastatic renal cell carcinoma (RCC).
The applicant for this medicinal product is Eisai Europe Ltd.
Kisplyx will be available as 4 mg and 10 mg hard capsules. The active substance of Kisplyx is lenvatinib, a tyrosine kinase inhibitor (ATC code: L01XE29) that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors, in addition to other proangiogenic and oncogenic pathway-related receptor tyrosine kinases.
Kisplyx was shown to improve progression-free survival (PFS) in a randomised part of a phase Ib/II study when used with everolimus (median 14.6 [95% CI: 5.9-20.1] months) compared with everolimus used alone (median 5.5 [95% CI: 3.5-7.1] months) with a HR of 0.40 (95% CI: 0.24, 0.68; p<0.001). The treatment effect of the combination was also supported by a post-hoc retrospective independent blinded review of scans with median PFS of 12.8 [95% CI: 7.4-17.5] months compared with everolimus used alone (median 5.6 [95% CI: 3.6-9.3] months) with a HR of 0.45 (95% CI: 0.26, 0.79; p=0.003).
The most common side effects are diarrhoea, fatigue, decreased appetite, vomiting, nausea and hypertension. Severe diarrhoea occurred at a higher frequency in the combination group than in the everolimus group.
The full indication is:
"Kisplyx is indicated in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior vascular endothelial growth factor (VEGF)-targeted therapy."
It is proposed that Kisplyx treatment should be initiated and supervised by a healthcare professional experienced in the use of anticancer therapies.
Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission. |
