近日，美国美国FDA宣布批准Imfinzi（durvalumab）用于治疗无法手术切除的III期非小细胞肺癌（NSCLC），且在铂类化疗和放疗同时治疗下病情没有进展的患者。
Durvalumab是一种程式死亡配体1 (PD-L1)阻断抗体，程式细胞死亡配体-1(PD-L1)的表达可能被炎症信号诱导(如，IFN-gamma)，和可能被表达在肿瘤细胞和在肿瘤微环境中肿瘤-关联免疫细胞上。PD-L1阻断T-细胞功能以及通过PD-1和CD80 (B7.1)作用相互活化。通过结合至它的受体，PD-L1减低细毒性T-细胞的活性，增殖，和细胞因数的产生。
Durvalumab是一种人免疫球蛋白G1 kappa (IgG1κ)单克隆抗体阻断PD-L1 与PD-1和CD80 (B7.1)的相互作用。 PD-L1/PD-1和PD-L1/CD80的相互作用能阻断释放免疫反应的抑制作用，无需诱导抗体依赖细胞-介导细胞毒性(ADCC)。
在同种移植的人类肿瘤和免疫细胞异种移植小鼠模型中，durvalumab阻断PD-L1能增加T-细胞的活化作用，减低肿瘤大小。
批准日期：2018年2月16日 公司：阿斯利康公司
IMFINZI（durvalumab）注射液，用于静脉注射
美国最初批准：2017年
最近的重大变化
适应症和用法，非小细胞肺癌：02/2018
剂量和给药，非小细胞肺癌：02/2018
警告和注意事项：02/2018
作用机制
程序性细胞死亡配体-1（PD-L1）的表达可以由炎性信号（例如，IFN-γ）诱导，并且可以在肿瘤微环境中的肿瘤细胞和肿瘤相关免疫细胞上表达。 PD-L1通过与PD-1和CD80的相互作用阻断T细胞功能和活化（B7.1）。通过与其受体结合，PD-L1降低细胞毒性T细胞活性，增殖和细胞因子产生。
Durvalumab是一种人免疫球蛋白G1 kappa（IgG1κ）单克隆抗体，可与PD-L1结合并阻断PD-L1与PD-1和CD80的相互作用（B7.1）。阻断PD-L1/PD-1和PD-L1/CD80相互作用释放免疫应答的抑制，而不诱导抗体依赖性细胞介导的细胞毒性（ADCC）。
使用durvalumab的PD-L1阻断导致体外T细胞活化增加并且共同移植的人肿瘤和免疫细胞异种移植小鼠模型中的肿瘤尺寸减小。
适应症和用法
IMFINZI是一种程序性死亡配体1（PD-L1）阻断抗体，用于治疗患者：
•局部晚期或转移性尿路上皮癌：
o在含铂化疗期间或之后有疾病进展。
o在使用含铂化疗的新辅助治疗或辅助治疗的12个月内有疾病进展。
根据肿瘤反应率和反应持续时间，在加速批准下批准该适应症。持续批准该适应症可能取决于确认试验中的临床益处的验证和描述。
•无法切除的III期非小细胞肺癌（NSCLC），其并发铂类化疗和放射治疗后疾病未发展。
剂量和给药
•尿路上皮癌：每2周10mg/kg。
•III期NSCLC：每2周10mg/kg。
剂量形式和强度
•注射：500mg/10mL（50mg/mL）溶液，单剂量小瓶。
•注射：单剂量小瓶中的120mg/2.4mL（50mg/mL）溶液。
禁忌症
没有。
警告和注意事项
•免疫介导的肺炎：对于严重或危及生命的肺炎，中度和永久性停用。
•免疫介导的肝炎：监测肝功能的变化。对于严重或危及生命的转氨酶或总胆红素升高的中度和永久性停用。
•免疫介导的结肠炎：对于严重或危及生命的结肠炎，保留中度和永久性停药。
•免疫介导的内分泌病：适用于中度，重度或危及生命的疾病。
•免疫介导的肾炎：监测肾功能的变化。对于严重或危及生命的肾炎，暂停中度和永久性停药。
•免疫介导的皮肤病学反应：对于严重或危及生命的皮疹，中度和永久性停药。
•感染：保留严重或危及生命的感染。
•输液相关反应：中度或减慢轻度或中度输注速度，并对严重或危及生命的输液相关反应永久停药。
•胚胎 - 胎儿毒性：可能导致胎儿伤害。告知女性有可能对胎儿造成潜在风险并使用有效避孕措施。
不良反应
•最常见的不良反应（≥15％的尿路上皮癌患者）是疲劳，肌肉骨骼疼痛，便秘，食欲减退，恶心，外周性水肿和尿路感染。
•最常见的不良反应（≥20％无法切除的III期NSCLC患者）为咳嗽，疲劳，肺炎/放射性肺炎，上呼吸道感染，呼吸困难和皮疹。
要报告疑似不良反应，请致电1-800-236-9933联系AstraZeneca或1-800-FDA-1088或WWW.FDA.GOV/MEDWATCH联系FDA。
用于特定人群
哺乳期：建议不要母乳喂养。
包装提供/存储和处理
IMFINZI（durvalumab）注射液是一种透明的乳白色，无色至微黄色溶液，装在一个装有一个单剂量小瓶的纸箱中，如下：
•500毫克/10毫升（NDC 0310-4611-50）
•120毫克/2.4毫升（NDC 0310-4500-12）
使用原装纸箱存放在2°C至8°C（36°F至46°F）的冰箱中，以防光照。
不要冻结。别摇了。
完整说明书资料附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3
Imfinzi(durvalumab)
Imfinzi(durvalumab) is an immunotherapy treatment, meaning it impacts the way the immune system functions. More specifically, it is a human monoclonal antibody that blocks the programmed death-ligand PD-L1.
It is indicated for use by adults with unresectable, Stage III NSCLC (non-small cell lung cancer) that has not progressed beyond the chest, nor following concurrent platinum-based chemotherapy and radiation therapy.
It is also indicated for use by individuals with specific types of bladder cancer, and is administered via an infusion.
Individuals taking Imfinzi should be monitored for pneumonitis (inflammation of the lungs), changes in liver function, intestinal problems, changes in kidney function, hormone changes, severe rashes, infections, and infusion-related reactions.
What are the ingredients in Imfinzi?
The active ingredient in Imfinzi is durvalumab, the PD-L1 blocker.
How does Imfinzi work?
Imfinzi blocks a programmed death-ligand, PD-L1. PD-L1 is a protein that plays a key role in regulating the immune system and immune response. PD-L1 binds to a receptor called PD-1 on specific immune system cells, including T cells and B cells. These cells normally attack foreign invaders, such as cancers. When PD-L1 and PD-1 join together, the immune system response is inhibited, or turned down, significantly. This process can happen in the body during pregnancy, or when an individual has an autoimmune condition or other condition like hepatitis. When the immune system is turned down, the chance of immune cells like T cells and B cells finding and eliminating cancer cells is decreased. Cancer cells can take advantage of this and can increase PD-1 and PD-L1 binding to avoid the protective cells of the immune system. Imfinzi blocks the joining of PD-1 and PD-L1 to keep the immune response from being suppressed.
What are the possible side effects of Imfinzi?
Multiple clinical trials eva luated the safety and efficacy of Imfinzi. The most common side effects of Imfinzi for individuals using it for treatment of NSCLC are fatigue, cough, radiation pneumonitis/pneumonitis, rash, problems breathing, and upper respiratory infections. This is not an exhaustive list of all potential side effects of Imfinzi. Talk to your healthcare provider or pharmacist for further information.
Things to note about Imfinzi
Imfinzi is an immunotherapy treatment that can impact the way the immune system functions, potentially leading to serious damage to other organs and tissues. Individuals taking Imfinzi should be monitored for the following complications:
Liver problems, including hepatitis
Lung problems, including pneumonitis
Intestinal problems, including colitis
Hormone gland problems, including issues with the thyroid, pituitary, pancreas, and adrenals
Kidney problems
Severe infections
Severe infusion reactions
It is also important to alert your doctor or healthcare provider if you notice any other new or worsening symptoms, including rash, confusion, mood or behavior changes, muscle weakness or pain, chest pain, shortness of breath, or difficulties with vision. These symptoms could be indicative of an issue with another organ or organ system.
The above signs and symptoms are not exhaustive of all indicators of potential issues. Talk to your doctor or healthcare provider if you are concerned about any new or worsening symptoms, even beyond the list above. Imfinzi is indicated for use by adults only. It is not indicated for use by women who are pregnant or breastfeeding.
Before starting Imfinzi, alert your provider if you:
Have liver problems
Have immune system problems including lupus, ulcerative colitis, or Crohn’s disease
Have breathing or lung problems
Have had an organ transplant
Currently have or are currently being treated for an infection
Are taking any other medications, including vitamins, over-the-counter medications, or herbal supplements
Have any other medical conditions
Are pregnant or could become pregnant
Are breastfeeding
Dosing information
Imfinzi is administered through an intravenous (IV) infusion into a vein. The infusion generally takes place over the course of an hour, however, the time of administration may be adjusted by your doctor or healthcare provider. The exact dosage and number of treatments will be determined by your doctor, however, a common dose and schedule is 10 mg/kg once every two weeks. Any missed infusion appointments need to be rescheduled as soon as possible.