FDA加快批准用于晚期软组织肉瘤新的治疗方法

近日，美国食品药品管理总局同意加快批准 Lartruvo (olaratumab)和多柔比星治疗某种软组织肉瘤，这种癌症是在肌肉、脂肪、肌腱或其他软组织发展的癌症。 Lartruvo被批准和FDA批准的化疗药物多柔比星共同用于治疗放疗或者手术不能治愈的软组织肉瘤病人，对于软组织肉瘤病人，蒽环类药物（化疗）是很合适的。

“对于这些病人，Lartruvo, 加多柔比星, 作为一个新的治疗方案，”Richard Pazdur说,（医学博士，FDA药品评估调查中心血液肿瘤产品办公室主任。美国食品和药物管理局肿瘤学中心代理主任。）“自从多柔比星批准超过40年后，这是个新的由FDA批准的用于软组织肉瘤的初步治疗药物。

国际癌症中心估计有12310个软组织肉瘤的新案例， 2016年近5000位死亡者可能死于这种疾病。对于不能手术移除的软组织肉瘤病人，常见的治疗是多柔比星单使用或与其他药物一起使用。软组织肉瘤包括在肌肉，脂肪，血管，神经，肌腱或关节的衬里生长的大量肿瘤。

Lartruvo是血小板衍生生长因子-受体α阻断抗体。当刺激时，血小板衍化生长因子受体引起肿瘤生长。Lartruvo 的作用就是阻隔这些受体，这药物可能会使肿瘤生长变慢或停止。

Lartruvo 的安全性和有效性在随机的临床试验中已经研究，涉及133个病人，25种不同的转移性软组织肉瘤子类型。病人服用Lartruvo 和多柔比星或者自服用多柔比星。这个试验测试了病人治疗后的生存时间（总生存期），治疗后肿瘤时间长度无增长（无进展生存期）及有癌症萎缩的患者比例（总的反应率）增长。这个试验中病人接受了Lartruvo和多柔比星，病人总生存期增长：平均生存时间26.5个月，而病人只服用多柔比星后只有14.7个月的生存期。病人接受了Lartruvo和多柔比星后中位无进展生存期是8.2个月，而病人只服用多柔比星的的生存期是4.4个月。病人服用Lartruvo和多柔比星后肿瘤缩小18.2%，而只服用多柔比星后肿瘤缩小7.5%。

服用Lartruvo可能会有严重的风险，其中包括积水-相关反应，胚胎和胎儿的危害。输注相关反应包括低血压，发烧，冷战和皮疹。Lartruvo 治疗常见的副作用是恶心，疲劳，白细胞减少（嗜中性白血球减少症），肌肉骨骼疼痛，粘膜炎症，脱发，呕吐，腹泻，食欲下降，胃疼，神经损伤和头疼。

FDA批准Lartruvo快车道申请，突破性疗法 设计和 优先审查 ，初步的临床证据显示治疗严重或危及生命的疾病情况下，它可能会提供实质性的改善。FDA加速审批批准Lartruvo 程序，允许批准用于治疗严重或威胁生命的疾病或病情。临床数据显示药物影响到替代性终点，很可能有临床获益。发起人正在进行一项更大的研究，现在还正在进行，通过对软组织肉瘤的多个亚型进行测试，进一步测试其有效性。   

  Lartruvo 也是一种罕见药，对其提供了优惠政策，例如税收抵免，家用户费用减免资格来帮助和鼓励药品的发展流通，用于治疗罕见疾病。

Lartruvo 由Eli Lilly公司提供，公司总部设在印第安纳波利斯印第安娜。(美域健康赵霞编译)

FDA grants accelerated approval to new treatment for advanced soft tissue sarcoma

For Immediate Release：October 19, 2016               FDA News Release

The U.S. Food and Drug Administration today granted accelerated approval to Lartruvo (olaratumab) with doxorubicin to treat adults with certain types of soft tissue sarcoma (STS), which are cancers that develop in muscles, fat, tendons or other soft tissues. Lartruvo is approved for use with the FDA-approved chemotherapy drug doxorubicin for the treatment of patients with STS who cannot be cured with radiation or surgery and who have a type of STS for which an anthracycline (chemotherapy) is an appropriate treatment.

“For these patients, Lartruvo, added to doxorubicin, provides a new treatment option,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and acting director of the FDA’s Oncology Center of Excellence. “This is the first new therapy approved by the FDA for the initial treatment of soft tissue sarcoma since doxorubicin’s approval more than 40 years ago.”

The National Cancer Institute estimates that 12,310 new cases of STS and nearly 5,000 deaths are likely to occur from the disease in 2016. The most common treatment for STS that cannot be removed by surgery is treatment with doxorubicin alone or with other drugs. STS includes a wide variety of tumors arising in the muscle, fat, blood vessels, nerves, tendons or the lining of the joints.

Lartruvo is a platelet-derived growth factor (PDGF) receptor-alpha blocking antibody. When stimulated, PDGF receptors cause tumor growth. Lartruvo works by blocking these receptors, which may help slow or stop tumor growth.

The safety and efficacy of Lartruvo were studied in a randomized clinical trial involving 133 patients with more than 25 different subtypes of metastatic STS. Patients received either Lartruvo with doxorubicin or doxorubicin alone. This trial measured the length of time patients lived after treatment (overall survival), the length of time tumors did not grow after treatment (progression-free survival) and the percentage of patients who experienced shrinkage of their tumors (overall response rate). Patients in this trial who received Lartruvo with doxorubicin had a statistically significant improvement in overall survival: the median survival was 26.5 months compared to 14.7 months for patients who received doxorubicin alone. Patients who received Lartruvo with doxorubicin had a median progression-free survival of 8.2 months compared to 4.4 months for patients who received doxorubicin alone. Tumor shrinkage was 18.2 percent for patients who received Lartruvo with doxorubicin and 7.5 percent for those who received doxorubicin alone.

Lartruvo has serious risks including infusion-related reactions and embryo-fetal harm. Infusion-related reactions include low blood pressure, fever, chills and rash. The most common side effects of treatment with Lartruvo are nausea, fatigue, low levels of white blood cells (neutropenia), musculoskeletal pain, inflammation of the mucous membranes (mucositis), hair loss (alopecia), vomiting, diarrhea, decreased appetite, abdominal pain, nerve damage (neuropathy) and headache.

The FDA granted the Lartruvo application fast track designation, breakthrough therapy designation and priority review status because preliminary clinical evidence indicated that it may offer a substantial improvement in effectiveness in the treatment of a serious or life-threatening disease or condition. The FDA is approving Lartruvo under the agency’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease or condition based on clinical data showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. The sponsor is conducting a larger study, which is currently underway, to further explore the effectiveness of Lartruvo across the multiple subtypes of STS.   

Lartruvo also received orphan drug designation, which provides incentives such as tax credits, user fee waivers and eligibility for exclusivity to assist and encourage the development of drugs intended to treat rare diseases.

Lartruvo is marketed by Eli Lilly and Company based in Indianapolis, Indiana.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.