新型抗癌药Portrazza(Necitumumab)静脉注射剂获美国FDA批准为用于特定类型（转移性鳞状-非小细胞肺癌）肺癌治疗 批准日期： 2015年11月24日；公司：Eli Lilly和公司 PORTRAZZA(necitumumab)注射液，为静脉使用 美国初次批准： 2015 作用机制 Necitumumab是一种重组人lgG1单克隆抗体结合至人表皮生长因子受体(EGFR)和阻断EGFR与其配体的结合。EGFR的表达和激活曾与恶性进展，血管生成的诱导，和凋亡的抑制作用相关。在体外Necitumumab的结合诱导EGFR内化和降解。在体外，在EGFR-表达细胞中necitumumab的结合还导致抗体-依赖性细胞细胞毒性(ADCC)。 在体内研究中使用人类癌的异种移植模型，包括非-小细胞肺癌，necitumumab的给予至被移植小鼠导致与吉西他滨和顺铂联用抗肿瘤活性与单独接受吉西他滨和顺铂比较增加抗肿瘤活性。 适应证和用途 PORTRAZZA™是一种表皮生长因子受体(EGFR)拮抗剂适用与吉西他滨和顺铂联用，为有转移鳞状非-小细胞肺癌患者首次线治疗。 使用限制： PORTRAZZA不适用为非-鳞状非-小细胞肺癌的治疗。 剂量和给药方法 PORTRAZZA的推荐剂量是800 mg(绝对剂量)为每3-周疗程在第1和8天在历时60分钟静脉输注。 剂型和规格 注射液：在单剂量小瓶中800mg/50mL(16mg/mL)溶液。 禁忌证 无。 警告和注意事项 心跳呼吸骤停：PORTRAZZA期间和后密切监视血清电解质。 低镁血症：PORTRAZZA每次输注前和完成后共至少8周监视。对3或4级电解质异常不给PORTRAZZA；在这些患者一旦电解质异常已改善至≤2级可能被给予PORTRAZZA的随后疗程。必要时补充电解质。 静脉和动脉血栓形成事件(VTE和ATE)：对严重VTE或ATE终止PORTRAZZA。 皮肤学毒性：监视皮肤学毒性和对严重毒性不给或终止PORTRAZZA。限制日光暴露。 输注相关反应： 输注期间和后监视体征和症状。对严重反应终止PORTRAZZA。 增加毒性：非-鳞状NSCLC -增加毒性和增加死亡率。 胚胎胎儿毒性：可能致胎儿危害。忠告生殖潜能妇女对胎儿的潜在风险和使用有效避孕。 不良反应 PORTRAZZA-治疗患者中观察到最常见不良反应(所有级别)在发生率≥30%和≥2%较高于单独吉西他滨和顺铂臂是皮疹和低镁血症。 报告怀疑不良反应，联系Eli Lilly和公司电话1-800-LillyRx(1-800-545-5979)或FDA电话1-800-FDA-1088或www.fda.gov/medwatch。 特殊人群中使用 哺乳：不要哺乳喂养。 供应/贮存和处置 供应 PORTRAZZA在单剂量小瓶中以无菌，无防腐剂溶液供应： ● 800mg/50mL(16mg/mL) NDC 0002-7716-01 贮存和处置 贮存小瓶在冰箱在2°至8°C(36°至46°F)直至使用时。为了避光保护将小瓶保存在外部纸盒。不要冻结或摇晃小瓶。 Portrazza (necitumumab) General Information Portrazza (necitumumab) is an epidermal growth factor receptor (EGFR) antagonist. Portrazza is specifically indicated for use in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer. Portrazza is supplied as a solution for intravenous administration. The recommended dose is 800 mg administered as an intravenous infusion over 60 minutes on Days 1 and 8 of each 3-week cycle prior to gemcitabine and cisplatin infusion. Continue until disease progression or unacceptable toxicity. Please see drug label for specific dose modifications. Clinical Results FDA Approval The FDA approval of Portrazza was based on SQUIRE ,an open-label, randomized, multi-center Phase III trial that compared first-line treatment with Portrazza in combination with gemcitabine and cisplatin to treatment with gemcitabine and cisplatin alone in 1,093 patients with metastatic squamous NSCLC. Patients on both arms of the study were allowed to receive a maximum of six cycles of chemotherapy. Patients on the Portrazza arm demonstrating at least stable disease continued to receive additional cycles of Portrazza until disease progression or unacceptable toxicity. Results showed a statistically significant improvement in overall survival over gemcitabine and cisplatin alone, specifically in the first-line setting. Portrazza combination therapy showed a statistically significant improvement in overall survival, the main outcome measure (p=0.01), with a median overall survival of 11.5 months for the Portrazza arm, as compared to 9.9 months for those treated with gemcitabine and cisplatin alone. This translated to a 16 percent reduction in risk of death. The percentage of deaths at the time of analysis was 77% on the Portrazza arm and 81% on the control arm. The significant survival improvement observed in SQUIRE was supported by a statistically significant improvement in progression-free survival (p=0.02), with a median progression-free survival (PFS) of 5.7 months on the Portrazza arm, as compared to 5.5 months for those treated with gemcitabine and cisplatin alone. The percentage of events at the time of analysis was 79% on the Portrazza arm and 76% on the control arm. Overall response rate (ORR) was also assessed and there was no difference between arms, with an ORR of 31% for the Portrazza plus gemcitabine and cisplatin arm and an ORR of 29% for the gemcitabine and cisplatin arm (p=0.40). Side Effects Adverse effects associated with the use of Portrazza may include, but are not limited to, the following: rash hypomagnesemia Portrazza comes with a boxed warning regarding the risk of cardiopulmonary arrest and hypomagnesemia. Mechanism of Action Portrazza (necitumumab) is a recombinant human lgG1 monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands. Expression and activation of EGFR has been correlated with malignant progression, induction of angiogenesis, and inhibition of apoptosis. Binding of necitumumab induces EGFR internalization and degradation in vitro. In vitro, binding of necitumumab also led to antibody-dependent cellular cytotoxicity (ADCC) in EGFR-expressing cells. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=89bcf553-669a-40b0-a9d7-67a5c1d2f591