腎癌葯Cabozantinib和Lenvatinib獲得歐盟認證

來自專欄 英度國際Cabozantinib and Lenvatinib for Kidney Cancer Get OK in EU

腎癌葯Cabozantinib和Lenvatinib獲得歐盟認證

Patients with kidney cancer in Europe who are not responding to treatment will soon have two new options to try, as cabozantinib (Cabometyx, Ipsen Pharma) and lenvatinib (Kisplyx, Eisai Europe Ltd) have been recommended for approval by the European Medicines Agency (EMA).

對治療沒有響應的歐洲腎癌患者，即將有兩種新的選擇可以嘗試。這是因為cabozantinib (Cabometyx, Ipsen Pharma) 和lenvatinib (Kisplyx, Eisai Europe Ltd)獲得了歐洲藥品局（EMA）的批准。

Both of these drugs are tyrosine kinase inhibitors, and both are recommended for use in patients with kidney cancer who have been previously treated with a vascular endothelial growth factor (VEGF) inhibitor. Cabozantinib is to be used as monotherapy, whereas lenvatinib is to be used in combination with everolimus (Afinitor, Novartis).

這兩種葯均為絡氨酸激酶抑製劑，兩者均推薦用於的先前接受過血管內皮生長因子（VEGF）抑製劑治療的腎癌患者。Cabozantinib用於單一治療，而lenvatinib需要與依維莫司（飛尼妥，諾華）聯合用藥。

The drugs are already approved for this indication in the United States.

藥物的適應症早已在美國獲得批准。

In its announcement, the EMA notes that the most common form of kidney cancer in adults is renal cell carcinoma (RCC). Advanced RCC includes both metastatic disease and locally advanced disease that cannot be removed by surgery. Despite the recent approval of new therapies for advanced RCC, many patients who do not respond to the existing treatments have a poor prognosis. Therefore, new treatment options are needed, the agency comments.

在它的說明中，EMA注意到成人最常見的腎癌類型為腎細胞癌（RCC）。晚期的RCC包括轉移性疾病和不能通過手術移除的局部晚期疾病。不管最近剛剛獲批的晚期RCC的新治療法如何，大多數對於正在進行的治療無響應的患者都有著不良的預後。所以，新的治療選擇是必須的，有機構如此評論道。

The EMA considers the kidney cancer indications for cabozantinib and lenvatinib to be accelerated approvals because both drugs were felt to address an unmet medical need.

EMA考慮到cabozantinib and lenvatinib的適應症是指向腎癌的，所以對其進行了加速審批。這是因為，這兩種葯能夠解決一個未被滿足的醫療需求。

The EMA also notes that both of these drugs are also used in thyroid cancer but are marketed for that indication under different trade names. Cabozantinib (as Cometriq) was approved in the EU in December 2013 for adults with medullary thyroid cancer, while lenvatinib (as Lenvima) was recommended for approval for patients with thyroid carcinoma in March 2015.

EMA也注意到了，這兩種藥物也都可以用於甲狀腺癌。但是在市場推廣中，不同的適應症使用不同的商品名。Cabozantinib (商品名 Cometriq)於2013年12月獲得EU批准，用於治療成人甲狀腺髓樣癌。而lenvatinib (商品名Lenvima)於2015年3月建議批准用於甲狀腺癌的患者。

Clinical Data to Support Approval

支持批准的臨床數據

Cabozantinib was recommended for approval mainly on the basis of a phase 3 trial (known as METEOR) involving 658 patients with metastatic RCC that had progressed after prior VEGF receptor tyrosine kinase inhibitor therapy. As previously reported by Medscape Medical News, this study showed the longest progression-free survival (PFS) ever seen in this setting, with 7.4 months on cabozantinib compared with 3.8 months on everolimus, which is the usual standard second-line therapy. In addition, preliminary results show an improved overall survival, with a median of 21.4 months on cabozantinib vs 16.5 months on everolimus.

Cabozantinib能夠建議批准，主要是基於它的3期臨床試驗（被稱作METEOR）。有658名在先前VEGF受體絡氨酸激酶抑製劑治療後發展的轉移性RCC患者參與其中。像先前Medscape Medical News報道中說道的，在此類設置中，這次研究表現出了最長的無進展生存期（PFS），Cabozantinib組為7.4個月，依維莫司組為3.8個月。其中，依維莫司通常用作標準二線治療。另外，其初步結果也表現出了對總存活數的提高，Cabozantinib組的中位數為21.4個月，而依維莫司組的為16.5個月。

The EMA notes that the most frequent adverse reactions associated with cabozantinib include diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (hand and foot redness, swelling, and pain), hypertension, and vomiting.

EMA也注意到，與cabozantinib相關的最常出現的不良反應包括腹瀉，疲乏，噁心，食慾降低，掌跖感覺喪失性紅斑綜合征（手腳發紅、發癢、疼痛），高血壓，和嘔吐。

Lenvatinib was recommended for approval mainly on the basis of a phase 1b/2 trial involving 153 patients with metastatic or unresectable RCC who received at least one prior VEGF targeted therapy and were treated with lenvatinib plus everolimus or with one of these agents used alone. In this study, progression-free survival was 12.8 months on average for patients receiving the combination of lenvatinib and everolimus, compared with 5.6 months for patients treated with everolimus alone, based on independent review of radiologic images. In addition, encouraging signs of prolonged overall survival were seen in patients given the combination therapy.

Lenvatinib能夠建議批准，主要是基於其1b/2期的臨床試驗。有153名先前至少接受過一次VEGF靶向治療的轉移性或不可切除的RCC患者參與其中，使用Lenvatinib和依維莫司進行治療，或者只使用其中一種藥物進行單獨治療。在這項研究中，聯用Lenvatinib和依維莫司治療的患者平均無進展存活期為12.8個月，而只使用依維莫司進行治療的患者只有5.6個月，基於放射學影像的獨立檢查。另外，對於進行聯合治療的患者，在總存活數的延長方面，有令人欣喜的跡象。

The most frequent adverse reactions include diarrhea, fatigue, decreased appetite, vomiting, nausea, and hypertension. Severe diarrhea occurred at a higher frequency in the combination group than in the everolimus group.

最常見的副反應包括腹瀉，疲乏，食慾降低，嘔吐，噁心，和高血壓。嚴重的腹瀉在聯合用藥組的發生率高於依維莫司組。

When assessing these data, the EMAs Committee for Medicinal Products for Human Use considered that the benefits of lenvatinib plus everolimus outweigh its risks but requested that postauthorization studies be conducted to collect further data to complement data from the phase 1b/2 trial.

在評估這些數據時，EMA人用醫學產品委員會考慮到lenvatinib和依維莫司的獲益勝過它的風險，但是同樣要求需要進行獲准後研究，以收集更多的數據完善1b/2期的臨床試驗中的數據。

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