2014.9.5FDA批准Keytruda用于晚期黑色素瘤治疗

FDA approves Keytrudafor advanced melanoma

药群论坛翻译稿：FDA批准Keytruda用于晚期黑色素瘤治疗

The U.S. Food andDrug Administration today granted accelerated approval to Keytruda(pembrolizumab) for treatment of patients with advanced or unresectablemelanoma who are no longer responding to other drugs.

译：FDA授予Keytruda (pembrolizumab)加速批准，用于其它疗法无效的晚期或不可切除的黑色素瘤的治疗。

Melanoma, which accounts for approximately 5 percent of all new cancers inthe United States, occurs when cancer cells form in skin cells that make thepigment responsible for color in the skin. According to the National CancerInstitute, an estimated 76,100 Americans will be diagnosed with melanoma and9,710 will die from the disease this year.

译：黑色素瘤发病率占美国新增肿瘤病例的5%，是源于皮肤中色素沉着区域的黑素细胞的恶性肿瘤，根据美国国家癌症研究所的统计数据，今年约有76,100例美国人被诊断对黑色素瘤患者，9,710例患者将死于此疾病。

Keytruda is the first approved drug that blocks acellular pathway known as PD-1, which restricts the body’s immune system fromattacking melanoma cells. Keytruda is intended for use following treatment withipilimumab, a type of immunotherapy. For melanoma patients whose tumors expressa gene mutation called BRAF V600, Keytruda is intended for use after treatmentwith ipilimumab and a BRAF inhibitor, a therapy that blocks activity of BRAFgene mutations.

译：Keytruda是第一个被批准的能阻断PD-1细胞通路的药物，PD-1能阻止人体免疫系统清除黑色素细胞。伊匹单抗（一种免疫调节药物）治疗无效的黑色素瘤患者可采用Keytruda治疗。另外，BRAF V600基因突变的黑色素瘤患者，经伊匹单抗和BRAF抑制剂治疗无效后可使用Keytruda。

“Keytruda is thesixth new melanoma treatment approved since 2011, a result of promisingadvances in melanoma research,” said Richard Pazdur, M.D., director of theOffice of Hematology and Oncology Products in the FDA’s Center for DrugEvaluation and Research. “Many of these treatments have different mechanisms ofaction and bring new options to patients with melanoma.”

译：FDA药品评估和研究中心血液学和肿瘤学产品办公室主任Richard Pazdur 博士称，Keytruda是2011年以来FDA批准的第六个用于黑色素瘤治疗的新药，这是黑色素瘤治疗研究发展的结果，这些基于不同作用机理的治疗药物为黑色素瘤患者带来了新的选择。

The five prior FDAapprovals for melanoma include: ipilimumab (2011), peginterferon alfa-2b(2011), vemurafenib (2011), dabrafenib (2013), and trametinib (2013).

译：FDA批准的另外五只黑色素瘤治疗药物包括：伊匹单抗（2011）、聚乙二醇干扰素α-2b（2011）、维罗非尼（2011）、达拉非尼（2013）和曲美替尼（2013）。

The FDA grantedKeytruda breakthrough therapy designation because the sponsordemonstrated through preliminary clinical evidence that the drug may offer asubstantial improvement over available therapies. It also received priorityreview and orphan product designation. Priority review is granted to drugs thathave the potential, at the time the application was submitted, to be asignificant improvement in safety or effectiveness in the treatment of aserious condition. Orphan product designation is given to drugs intended totreat rare diseases.

译：根据前期初步的临床结果，该药物可能会极大克服现有治疗手段的局限性，因此FDA授予Keytruda突破性疗法资格，并且给予了优先审查和孤儿药资格认证。优先审查是授予有潜力的，治疗恶性疾病的有效性和安全性有明显改善的候选药物，孤儿药资格是授予治疗罕见病的候选药物。

The FDA action was taken under the agency’s accelerated approval program,which allows approval of a drug to treat a serious or life-threatening diseasebased on clinical data showing the drug has an effect on a surrogate endpointreasonably likely to predict clinical benefit to patients. This programprovides earlier patient access to promising new drugs while the company conductsconfirmatory clinical trials. An improvement in survival or disease-relatedsymptoms has not yet been established.

译：FDA通过加速审评批准Keytruda，依据临床试验的替代终点，预测候选药物对严重的或者危及生命疾病的临床获益，这种审评程序能够使早期患者能够尽早使用有效的新药，同时，因生存或疾病相关症状改善与药物关系尚未完全确立，申请人要继续开展验证性的临床试验。

Keytruda’s efficacywas established in 173 clinical trial participants with advanced melanoma whosedisease progressed after prior treatment. All participants were treated withKeytruda, either at the recommended dose of 2 milligrams per kilogram (mg/kg)or at a higher dose of 10 mg/kg. In the half of the participants who receivedKeytruda at the recommended dose of 2 mg/kg, approximately 24 percent had theirtumors shrink. This effect lasted at least 1.4 to 8.5 monthsand continued beyond this period in most patients. A similarpercentage of patients had their tumor shrink at the 10 mg/kg dose.

译：Keytruda的有效性判断是基于173例标准治疗无效的晚期黑色素瘤患者治疗结果。所有受试者给予2 mg/kg或10 mg/kg Keytruda，一半接受2 mg/kg Keytruda治疗的受试者肿瘤体积减少了24%，效应持续了1.4-8.5个月，并且大多数患者有持续改善的趋势，10 mg/kg 组结果与此类似。

Keytruda’s safetywas established in the trial population of 411 participants with advancedmelanoma. The most common side effects of Keytruda were fatigue, cough, nausea,itchy skin (pruritus), rash, decreased appetite, constipation, joint pain(arthralgia) and diarrhea. Keytruda also has the potential for severeimmune-mediated side effects. In the 411 participants with advanced melanoma,severe immune-mediated side effects involving healthy organs, including thelung, colon, hormone-producing glands and liver, occurred uncommonly.

译：Keytruda的安全性评价是基于一项411例晚期黑色素瘤患者参与的临床试验，Keytruda常见的副作用包括疲劳、咳嗽、恶心、皮肤瘙痒、皮疹、食欲减轻、便秘、关节痛和腹泻。另外，411例受试者试验结果显示，Keytruda具有潜在的免疫介导的严重副作用，包括健康器官，例如肺、结肠、激素分泌腺体和肝脏，但是发生率极低。

Keytruda ismarketed by Merck & Co., based in Whitehouse Station, New Jersey.

译：Keytruda生产商是默克。