近日，PD-1药物Opdivo(nivolumab)静脉注射液已被美国FDA扩展批准治疗有晚期(转移)鳞状细胞非小细胞肺癌(NSCLC)用基于铂化疗或后有进展患者。 在美国肺癌是是癌症死亡的领先原因，在2014年有估计224,210例新诊断和159,260例死亡。肺癌的最常见型，NSCLC影响7/8肺癌患者，当在肺的细胞中癌形成时发生。 Opdivo通过抑制细胞通路被称为细胞上PD-1蛋白它阻断机体免疫系统攻击癌细胞起作用。Opdivo是意向为以前曾用基于铂化疗治疗患者。 FDA的药品评价和研究中心内血液学和肿瘤学产品室主任Richard Pazdur，M.D.说：“当2014年12月这个临床试验结果首次可得到时，FDA主动与公司工作有利于这个早期递交和审评，”“这个批准将为患者和卫生保健提供者提供伴随Opdivo生存获益的知识和将有助于指导患者医护和未来肺癌试验。” 批准日期：2015年3月4日 公司：百时美施贵宝（BMS）公司 OPDIVO（nivolumab）注射液，用于静脉注射 美国最初批准：2014年 最近的重大变化 适应症和用法：4/2018 剂量和用法：4/2018 警告和注意事项：4/2018 作用机制 PD-1配体，PD-L1和PD-L2与T细胞上发现的PD-1受体的结合抑制T细胞增殖和细胞因子产生。在一些肿瘤中发生PD-1配体的上调，并且通过该途径的信号传导可以有助于抑制肿瘤的活性T细胞免疫监视。 Nivolumab是一种人免疫球蛋白G4（IgG4）单克隆抗体，可与PD-1受体结合并阻断其与PD-L1和PD-L2的相互作用，释放PD-1途径介导的免疫应答抑制，包括抗肿瘤免疫应答。 在同系小鼠肿瘤模型中，阻断PD-1活性导致肿瘤生长减少。 联合nivolumab（抗PD-1）和ipilimumab（抗-CTLA-4）介导的抑制作用增强T细胞功能，其大于单独任一抗体的作用，并导致改善的转移性黑素瘤和晚期RCC的抗肿瘤反应。在鼠syngeneictumor模型中，PD-1和CTLA-4的双重阻断导致抗肿瘤活性增加。 适应症和用法 OPDIVO是程序性死亡受体-1（PD-1）阻断抗体，其用于治疗：患有BRAF V600野生型不可切除或转移性黑素瘤的患者，作为单一药剂。 BRAF V600突变阳性患者无法切除或转移 黑色素瘤，作为单一药物。患有不可切除或转移性黑色素瘤的患者，与皮利姆单抗联合使用。 在辅助治疗中，患有淋巴结受累或转移性疾病的黑色素瘤患者已经完全切除。 转移性非小细胞肺癌患者和铂类化疗后的进展。患有EGFR或ALK基因组畸变的患者在接受OPDIVO之前应该在FDA批准的治疗这些畸变的疾病进展。 已接受过抗血管生成治疗的晚期肾细胞癌患者。 患有中度或低风险的患者，既往未治疗的晚期肾细胞癌，与ipilimumab联合使用。 具有复发或进展的经典霍奇金淋巴瘤的成年患者：自体造血干细胞移植（HSCT）和非伦妥昔单抗vedotin，或包括自体HSCT的3或更多系统性治疗。 患有复发性或转移性头颈部鳞状细胞癌的患者，在铂类治疗之后或之后疾病进展。 患有局部晚期或转移性尿路上皮癌的患者：在含铂化疗的新辅助治疗或辅助治疗的12个月内，在含铂化疗期间或之后疾病进展有疾病进展。 患有微卫星不稳定性-高（MSI-H）或错配修复缺陷（dMMR）转移性结直肠癌的成人和儿科（12岁及以上）患者，其在用氟嘧啶，奥沙利铂和伊立替康治疗后进展。 已经使用索拉非尼治疗的肝细胞癌患者该指征在无进展生存的加速批准下获得批准。在验证试验中验证和描述临床获益后，可继续批准该适应症。该指征根据总体反应率和反应持续时间在加速批准下批准。持续批准此指示可能取决于确认试验中的临床效益的验证和描述。 剂量和给药 在30分钟内将OPDIVO作为静脉输注给药。 不可切除或转移性黑素瘤OPDIVO每2周240mg或每4周480mg。 使用ipilimumab的OPDIVO：OPDIVO 1mg/kg，然后在同一天使用ipilimumab，每3周一次，共4剂，然后每2周OPDIVO 240mg或每4周480mg。 辅助治疗黑色素瘤 OPDIVO每2周240毫克或每4周480毫克。 转移性非小细胞肺癌 OPDIVO每2周240毫克或每4周480毫克。 晚期肾细胞癌 OPDIVO每2周240毫克或每4周480毫克。 使用ipilimumab的OPDIVO：OPDIVO 3mg/kg，然后每3周在同一天ipilimumab 1mg/kg，共4剂，然后每2周OPDIVO 240mg或每4周480mg。 经典霍奇金淋巴瘤 OPDIVO每2周240毫克或每4周480毫克。 头颈部复发或转移性鳞状细胞癌 OPDIVO每2周240毫克或每4周480毫克。 局部晚期或转移性尿路上皮癌 OPDIVO每2周240毫克或每4周480毫克。 微卫星不稳定性高（MSI-H）或错配修复缺陷（dMMR）转移性结直肠癌 OPDIVO每2周240毫克。 肝细胞癌 OPDIVO每2周240毫克或每4周480毫克。 剂量形式和强度 注射：40mg/4mL，100mg/10mL和240mg/24mL溶液在单一化疗中。 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。 免疫介导的结肠炎：当作为中度或重度的单一药剂给予时，扣留OPDIVO并且永久性地停止用于危及生命的结肠炎。ipilimumab给予OPDIVO用于中度和永久性停用严重或危及生命的结肠炎。 免疫介导的肝炎：监测肝功能的变化。保留适度和永久性中断严重或危及生命 转氨酶或总胆红素升高。 免疫介导的内分泌疾病：保留中度或重度并永久性地停止危及生命的垂体炎。对于严重或危及生命的肾上腺功能不全,不得停止使用。监测甲状腺功能的变化。根据需要启动甲状腺激素替代治疗。监测高血糖。对于危及生命的高血糖症，请坚持不懈并永久停止服用。 免疫介导的肾炎和肾功能不全：监测肾功能的变化。保留中度或重度并永久性地停止威胁生命的血清肌酐升高。 免疫介导的皮肤不良反应：坚持严重和永久性地停止危及生命的皮疹。 免疫介导的脑炎：监测神经功能的变化。 保留新发中度至重度神经系统体征或症状，并永久停止免疫介导的脑炎。 输液反应：停止OPDIVO用于严重和危及生命的输注反应。中度或缓慢轻度或中度输液反应患者的输注速度。 OPDIVO后同种异体HSCT的并发症：监测超急性移植物抗宿主病（GVHD），3-4级急性GVHD，甾体感染性发热综合征，肝静脉闭塞性疾病和其他免疫介导的不良反应。与移植相关的死亡率已经发生。 胚胎-胎儿毒性：可导致胎儿伤害。建议潜在的潜在风险和使用有效的避孕措施。 不良反应 患者最常见的不良反应（20％）为：OPDIVO作为单一药物：疲劳，皮疹，肌肉骨骼疼痛，瘙痒，腹泻，恶心，虚弱，咳嗽，呼吸困难，便秘，食欲减退，背痛，关节痛，上呼吸道肠道感染，发热，头痛和腹痛。 用ipilimumab治疗黑色素瘤的OPDIVO：疲劳，皮疹，腹泻，恶心，发热，呕吐和呼吸困难。 用ipilimumab治疗肾细胞癌的OPDIVO：疲劳，皮疹，腹泻，肌肉骨骼疼痛，瘙痒，恶心，咳嗽，发热，关节痛和食欲下降。 用于特定人群 哺乳期：停止母乳喂养。 包装提供/存储和处理 OPDIVO（nivolumab）注射剂如下： 纸箱内容NDC 40mg/4mL单剂量小瓶0003-3772-11 100mg/10mL单剂量小瓶0003-3774-12 240mg/24mL单剂量小瓶0003-3734-13 将OPDIVO储存在2°C至8°C（36°F至46°F）的冷藏温度下。 保护OPDIVO免受光照存放在原始包装中直到使用。 不要冻结或摇晃。 完整资料附件：https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125554s058lbl.pdf Opdivo(nivolumab injection) FULL INDICATIONS For Previously Treated Patients With Advanced Non-Small Cell Lung Cancer (1 of 12) OPDIVO® (nivolumab) is a prescription medicine used to treat people with a type of advanced stage lung cancer (called non-small cell lung cancer) that has spread or grown and you have tried chemotherapy that contains platinum, and it did not work or is no longer working. If your tumor has an abnormal EGFR or ALK gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working. It is not known if OPDIVO is safe and effective in children younger than 18 years of age. For Previously Treated Patients With Advanced Small Cell Lung Cancer (2 of 12) OPDIVO® (nivolumab) is a prescription medicine used to treat people with a type of advanced stage lung cancer (called small cell lung cancer) that has spread or grown and you have tried at least two different types of chemotherapy, including one that contains platinum, and it did not work or is no longer working. OPDIVO was approved based on response rate and how long patients’ responses lasted. There is ongoing evaluation of clinical benefit of OPDIVO for this use. It is not known if OPDIVO is safe and effective in children younger than 18 years of age. For Patients With Metastatic Melanoma (3 of 12) OPDIVO® (nivolumab) is a prescription medicine used to treat people with a type of skin cancer called melanoma that has spread or cannot be removed by surgery (advanced melanoma). OPDIVO is approved for both BRAF+ and BRAF- patients. OPDIVO was approved for BRAF+ metastatic melanoma patients based on the amount of time patients lived without their tumors worsening. There is ongoing evaluation of clinical benefit of OPDIVO for this use. OPDIVO® (nivolumab) is a prescription medicine used in combination with YERVOY® (ipilimumab) to treat people with a type of skin cancer called melanoma that has spread or cannot be removed by surgery (advanced melanoma). OPDIVO in combination with YERVOY was approved based on the amount of time patients lived without their tumors worsening. There is ongoing evaluation of clinical benefit of OPDIVO in combination with YERVOY for this use. It is not known if OPDIVO is safe and effective in children younger than 18 years of age. To Help Prevent a Skin Cancer Called Melanoma From Coming Back After It and the Affected Lymph Nodes Have Been Removed by Surgery (4 of 12) OPDIVO® (nivolumab) is a prescription medicine used to treat people with a type of skin cancer called melanoma to help prevent melanoma from coming back after it and lymph nodes that contain cancer have been removed by surgery. It is not known if OPDIVO is safe and effective in children younger than 18 years of age. For Adults With Kidney Cancer (Renal Cell Carcinoma) That Has Spread (5 of 12) OPDIVO® (nivolumab) is a prescription medicine used in combination with YERVOY® (ipilimumab) to treat kidney cancer (renal cell carcinoma) in certain people when their cancer has spread. It is not known if OPDIVO is safe and effective in children younger than 18 years of age. OPDIVO (10mg/mL) and YERVOY (5 mg/mL) are injections for intravenous (IV) use. For Previously Treated Patients With Advanced Renal Cell Carcinoma (6 of 12) OPDIVO® (nivolumab) is a prescription medicine used to treat people with kidney cancer (renal cell carcinoma) when your cancer has spread or grown after treatment with other cancer medications. It is not known if OPDIVO is safe and effective in children younger than 18 years of age. For Patients With Squamous Cell Carcinoma of the Head and Neck (SCCHN) That Has Returned or Spread After Previous Treatment (7 of 12) OPDIVO® (nivolumab) is a prescription medicine used to treat people with head and neck cancer (squamous cell carcinoma) that has come back or spread and you have tried chemotherapy that contains platinum and it did not work or is no longer working. It is not known if OPDIVO is safe and effective in children younger than 18 years of age. For People With Liver Cancer (Hepatocellular Carcinoma) That Have Received Treatment With Nexavar® (sorafenib) (8 of 12) OPDIVO® (nivolumab) is a prescription medicine used to treat people with liver cancer (hepatocellular carcinoma) after you have received treatment with Nexavar® (sorafenib). OPDIVO was approved based on response rate and how long patients’ responses lasted. There is ongoing evaluation of clinical benefit of OPDIVO for this use. It is not known if OPDIVO is safe and effective in children younger than 18 years of age. For Previously Treated Patients With Advanced Bladder Cancer (Urothelial Carcinoma) (9 of 12) OPDIVO® (nivolumab) is a prescription medicine used to treat people with bladder cancer (urothelial carcinoma) that has spread or grown and you have tried chemotherapy that contains platinum, and it did not work or is no longer working. OPDIVO was approved based on response rate and how long patients’ responses lasted. There is ongoing evaluation of clinical benefit of OPDIVO for this use. It is not known if OPDIVO is safe and effective in children younger than 18 years of age. For Adults Whose CRC Has Spread to Other Parts of the Body (Metastatic), Has Progressed After Treatment With a Fluoropyrimidine, Oxaliplatin, and Irinotecan, and is dMMR or MSI-H (10 of 12) OPDIVO® (nivolumab) is a prescription medicine used in combination with YERVOY® (ipilimumab) to treat adults and children 12 years of age and older, with a type of colon or rectal cancer (colorectal cancer) that has spread to other parts of the body (metastatic), is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), and you have tried treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, and it did not work or is no longer working. OPDIVO was approved based on response rate and how long patients’ responses lasted. There is ongoing evaluation of clinical benefit of OPDIVO for this use. It is not known if OPDIVO is safe and effective in children younger than 12 years of age with MSI-H or dMMR metastatic colorectal cancer. OPDIVO (10mg/mL) and YERVOY (5mg/mL) are injections for intravenous (IV) use. For People 12 Years of Age and Older Whose CRC Has Spread to Other Parts of the Body (Metastatic), Has Progressed After Treatment With a Fluoropyrimidine, Oxaliplatin, and Irinotecan, and Is dMMR or MSI-H (11 of 12) OPDIVO® (nivolumab) is a prescription medicine used to treat adults and children 12 years of age and older with a type of colon or rectal cancer (colorectal cancer) that has spread to other parts of the body (metastatic), is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), and you have tried treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, and it did not work or is no longer working. OPDIVO was approved based on response rate and how long patients’ responses lasted. There is ongoing evaluation of clinical benefit of OPDIVO for this use. It is not known if OPDIVO is safe and effective in children younger than 12 years of age with MSI-H or dMMR metastatic colorectal cancer. For Adults With classical Hodgkin Lymphoma Whose Cancer Has Come Back or Spread After an Autologous Stem Cell Transplant and Treatment With Adcetris® (brentuximab vedotin) or After 3 or More Kinds of Treatment Including an Autologous Stem Cell Transplant (12 of 12) OPDIVO® (nivolumab) is a prescription medicine used to treat adults with a type of blood cancer called classical Hodgkin Lymphoma if your cancer has come back or spread after a type of stem cell transplant that uses your own stem cells (autologous), and you used the drug brentuximab vedotin (Adcetris®) before or after your stem cell transplant, or if you received at least 3 kinds of treatment including an autologous stem cell transplant. OPDIVO was approved based on response rate. There is ongoing evaluation of clinical benefit of OPDIVO for this use. It is not known if OPDIVO is safe and effective in children younger than 18 years of age. It is not known if OPDIVO is safe and effective in children younger than 12 years of age with MSI-H or dMMR metastatic colorectal cancer, or in children younger than 18 years of age for the treatment of any other cancers.