新类型抗癌药Tecentriq（atezolizumab 中文暂定药名：阿特朱单抗）已被FDA批准的首个和唯一的抗PD-L1癌症免疫药物，也是30年来FDA首个批准特定类型膀胱癌针对性治疗药。同时还批准了Tecentriq辅助诊断试剂Ventana PD-L1 (SP142)分析试剂盒。 2016年5月18日，美国FDA批准了Tecentriq（atezolizumab）用于治疗尿路上皮癌，这是首个获准治疗这类癌症的PD-1/PD-L1抑制剂类新药。FDA同时还批准了Tecentriq辅助诊断试剂Ventana PD-L1 (SP142)分析试剂盒，用于测定肿瘤浸润免疫细胞PD-L1表达水平。 FDA药品评价暨研究中心血液与肿瘤产品办公室主任Richard Pazdur博士指出：“Tecentriq为这些患者提供了一种新的PD-L1通路靶向治疗药物”。“阻断PD-1/PD-L1相互作用的产品是人类不断认识人体免疫系统与肿瘤细胞相互关系发展过程的一部分。” Tecentriq靶向阻断PD-1/PD-L1通路，有助于人体免疫系统攻击肿瘤细胞。Tecentriq是FDA批准的首个PD-L1抑制剂，也是近两年批准的最新PD-1/PD-L1靶向生物制剂。 Tecentriq获准用于治疗含铂类药物化疗治疗期间或治疗后疾病恶化，或者术前（新辅助治疗）或术后（辅助治疗）接受含铂类药物化疗12个月内疾病恶化的局部晚期或转移性尿路上皮癌患者。尿路上皮癌是最常见的膀胱癌类型，发生于尿路系统，累及膀胱及其相关器官。据美国国立癌症研究所估计，2016年新增膀胱癌患者76,960例，死亡16,390例。 Tecentriq的安全性和有效性透过一项纳入310例局部晚期或转移性尿路上皮癌的单臂临床研究进行了评价。总体上，肿瘤出现全部或部分缩小的患者比例（客观应答率）为14.8%，该作用可持续2.1~13.8个月。PD-L1表达阳性患者，应答率提高至26%，这表明PD-L1表达水平有助于医生识别哪些患者可能从Tecentriq治疗中获益更大。因此FDA同时批准了Tecentriq辅助诊断试剂Ventana PD-L1 (SP142)分析试剂盒。 Tencentriq治疗最常见的副作用为疲劳、食欲下降、恶心、尿路感染、发热以及便秘。Tencentriq对免疫系统的作用还可能导致感染和严重副作用，累及肺、结肠和内分泌系统等。 General Information Tecentriq (atezolizumab) is a programmed death-ligand 1 (PD-L1) blocking antibody. Tecentriq is specifically indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who: Have disease progression during or following platinum-containing chemotherapy  Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy Tecentriq is supplied as a solution for intravenous injection. The recommended dose is 1200 mg as an intravenous infusion over 60 minutes every 3 weeks. TECENTRIQ Rx Generic Name and Formulations: Atezolizumab 60mg/mL; soln for IV infusion after dilution; preservative-free. Company: Genentech, Inc. Indications for TECENTRIQ: Treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Adult: Give as IV infusion over 60mins. 1200mg every 3 weeks until disease progression or unacceptable toxicity. May give subsequent infusions over 30mins if first infusion tolerated. Children: Not established. Warnings/Precautions: Permanently discontinue if Grade 3/4 pneumonitis, AST or ALT >5×ULN or total bilirubin >3×ULN, Grade 4 diarrhea or colitis, Grade 4 hypophysitis, myasthenic syndrome/myasthenia gravis, Guillain-Barre or meningoencephalitis, Grade 3/4 ocular inflammatory toxicity, Grade 4 or recurrent pancreatitis, Grade 3/4 infusion-related reactions, or Grade 4 rash. Withhold for Grade 2 pneumonitis, AST or ALT >3–5×ULN or total bilirubin >1.5–3×ULN, Grade 2/3 diarrhea or colitis, symptomatic hypophysitis, adrenal insufficiency, hypothyroidism, hyperthyroidism, Grade 3/4 hyperglycemia, Grade 2 ocular inflammatory toxicity, Grade 2/3 pancreatitis or Grade 3/4 increases in amylase or lipase levels (>2×ULN), Grade 3/4 infection, Grade 2 infusion-related reactions, or Grade 3 rash; may be resumed when recover to Grade 0–1. Monitor for immune-related pneumonitis, hepatitis (obtain AST, ALT, bilirubin prior to and during treatment), diarrhea/colitis, endocrinopathies (hypophysitis, thyroid function, adrenal insufficiency, diabetes), meningitis or encephalitis, motor and sensory neuropathy, and acute pancreatitis; see full labeling for adverse reaction management details. Monitor for signs/symptoms of infection and treat with antibiotics for suspected or confirmed bacterial infections. Interrupt or slow the infusion rate in patients with mild or moderate infusion reactions. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity. Pregnancy. Use effective contraception during and for ≥5 months after final dose. Nursing mothers: not recommended (during and for ≥5 months after final dose). Pharmacological Class: PD-L1 inhibitor. Adverse Reactions: Fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, constipation; lab abnormalities. Generic Availability: NO How Supplied: Single-dose vial (20mL)—1 罗氏PD-L1免疫疗法Tecentriq非小细胞肺癌的III期临床研究 2016年9月5日，瑞士制药巨头罗氏（Roche）近日公布了PD-L1肿瘤免疫疗法Tecentriq（atezolizumab）肺癌III期OAK研究的积极数据。该研究在接受含铂化疗治疗过程中或治疗后病情进展的局部晚期或转移性非小细胞肺癌（NSCLC）患者中开展，数据显示，与多西他赛（docetaxel）化疗相比，Tecentriq使总生存期（OS）实现了统计学意义和临床意义的显著改善，达到了研究的共同主要终点。该研究中所观察到的不良事件与之前Tecentriq研究中的一致。罗氏计划在2016年即将召开的医学会议上公布该研究的完整数据。 之前，FDA已授予Tecentriq治疗PD-L1（程序性死亡配体1）阳性非小细胞肺癌（NSCLC）的突破性药物资格（BTD），同时授予Tecentriq治疗NSCLC生物制品许可申请（BLA）的优先审查资格，并将于2016年10月19日作出最终审查决定。 目前，罗氏正在开展8个III期临床研究，评估Tecentriq单药疗法或联合其他药物，用于早期及晚期阶段肺癌的治疗。 atezolizumab是一种实验性全人源化单克隆抗体，旨在靶向肿瘤细胞和肿瘤浸润免疫细胞表面表达的PD-L1蛋白，阻止其与T细胞表面的PD-1和B7.1受体结合。通过抑制PD-L1，atezolizumab能够使T细胞激活。 今年5月，FDA加速批准Tecentriq用于治疗最常见类型的膀胱癌——尿路上皮膀胱癌，该药也由此成为FDA批准的首个抗PD-L1抑制剂；同时，尿路上皮膀胱癌也是Tecentriq在监管方面收获的首个批文。 目前，罗氏正在积极推进一个庞大的临床开发项目，调查atezolizumab治疗特定类型肺癌、肾癌、乳腺癌和膀胱癌的潜力。同时，罗氏也正在努力推进atezolizumab与其他药物的组合疗法，以挖掘该药的最大临床潜力 TECENTRIQ®THE FIRST AND ONLY FDA-APPROVED ANTI-PDL1 CANCER IMMUNOTHERAPY INDICATIONS Locally advanced or metastatic urothelial carcinoma TECENTRIQ (atezolizumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who: •Have disease progression during or following platinum-containing chemotherapy •Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Metastatic non-small cell lung cancer TECENTRIQ is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving TECENTRIQ. ALK=anaplastic lymphoma kinase; EGFR=epidermal growth factor receptor; PD-L1=programmed death-ligand 1. IMPORTANT SAFETY INFORMATION Serious Adverse Reactions Please refer to the full Prescribing Information for important dose management information specific to adverse reactions. Immune-Related Pneumonitis •Immune-related pneumonitis or interstitial lung disease, including 2 fatal cases, occurred with TECENTRIQ treatment •Pneumonitis occurred in 3.7% of patients with non-small cell lung cancer (NSCLC) and 1.1% of patients with urothelial cancer (UC) •Monitor patients for signs with radiographic imaging and symptoms of pneumonitis. Administer steroids for Grade 2 or greater pneumonitis. Withhold TECENTRIQ until resolution for Grade 2 pneumonitis. Permanently discontinue for Grade 3 or 4 pneumonitis Immune-Related Hepatitis •Immune-mediated hepatitis, including a fatal case in urothelial carcinoma (UC), and liver test abnormalities have occurred with TECENTRIQ treatment •Across clinical trials, Grade 3 or 4 elevation occurred in ALT (2.5%), AST (2.3%), and total bilirubin (1.6%). Immune-mediated hepatitis occurred in 1.3% of patients with UC and 0.9% of patients with NSCLC •Monitor patients for signs and symptoms of hepatitis. Monitor AST, ALT, and bilirubin prior to and periodically during treatment •Administer corticosteroids for Grade 2 or greater transaminase elevations, with or without concomitant elevation in total bilirubin. Withhold TECENTRIQ for Grade 2, and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis Immune-Related Colitis •Immune-related colitis, including a fatal case of diarrhea-associated renal failure, have occurred with TECENTRIQ treatment •Across clinical trials, colitis or diarrhea occurred in 19.7% of patients •Immune-mediated colitis or diarrhea occurred in 0.8% of patients with UC and 0.5% of patients with NSCLC •Monitor patients for signs and symptoms of diarrhea or colitis. Withhold TECENTRIQ for Grade 2 or Grade 3 diarrhea or colitis. Permanently discontinue for Grade 4 diarrhea or colitis Immune-Related Endocrinopathies •Immune-related thyroid disorders, adrenal insufficiency, hypophysitis, and type 1 diabetes mellitus, including diabetic ketoacidosis, have occurred in patients receiving TECENTRIQ. Monitor patients for clinical signs and symptoms of endocrinopathies •Across clinical trials, hypo- and hyperthyroidism occurred in 3.9% and 1.0% of patients, respectively. In patients with NSCLC, hypo- and hyperthyroidism occurred in 4.2% and 1.1%, respectively. Monitor thyroid function prior to and periodically during treatment with TECENTRIQ. For symptomatic hypothyroidism, withhold TECENTRIQ and initiate hormone replacement as needed. Manage isolated hypothyroidism with replacement therapy and without corticosteroids. For symptomatic hyperthyroidism, withhold TECENTRIQ and initiate an anti-thyroid drug as needed •Across clinical trials, adrenal insufficiency occurred in 0.4% of patients. For symptomatic adrenal insufficiency, withhold TECENTRIQ and administer steroids •In UC, hypophysitis occurred in 0.2% of patients. Administer corticosteroids and hormone replacement as clinically indicated. Withhold for Grade 2 or Grade 3, and permanently discontinue for Grade 4 hypophysitis •New onset diabetes with ketoacidosis occurred in patients. Diabetes mellitus without an alternative etiology occurred in 0.3% of patients with NSCLC. Initiate treatment with insulin for type 1 diabetes mellitus. For ≥Grade 3 hyperglycemia (fasting glucose >250-500 mg/dL), withhold TECENTRIQ Other Immune-Related Adverse Reactions •Other immune-related adverse reactions, including meningoencephalitis, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, ocular inflammatory toxicity, and pancreatitis, including increases in serum amylase and lipase levels, have occurred in ≤1.0% of patients treated with TECENTRIQ •Symptomatic pancreatitis without an alternative etiology occurred in 0.1% of patients across clinical trials •Monitor patients for clinical signs and symptoms of meningitis or encephalitis, as well as symptoms of motor and sensory neuropathy. Permanently discontinue TECENTRIQ for any grade of meningitis or encephalitis, or any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome •Monitor patients for signs and symptoms of acute pancreatitis. Withhold TECENTRIQ for ≥Grade 3 serum amylase or lipase levels (>2.0 ULN), or Grade 2 or 3 pancreatitis. Permanently discontinue for Grade 4 or any grade of recurrent pancreatitis Infection •Severe infections, including sepsis, herpes encephalitis, and mycobacterial infection leading to retroperitoneal hemorrhage, occurred in patients receiving TECENTRIQ •In UC, infection occurred in 37.7% of patients. Grade 3 or 4 infection occurred in 11.5% of patients, while 3 patients died due to infections. Urinary tract infections were the most common cause of Grade 3 or higher infection, occurring in 7.1% of patients •In a NSCLC study, infection occurred in 43% (Grade 3 or 4 was 9.2%) of patients treated with TECENTRIQ compared with 34% (Grade 3 or 4 was 2.2%) with docetaxel. Two patients died due to infections. Pneumonia was the most common cause of Grade 3 or higher infection, occurring in 7.7% of patients •Monitor patients for signs and symptoms of infection and treat with antibiotics for suspected or confirmed bacterial infections. Withhold TECENTRIQ for ≥Grade 3 infection Infusion-Related Reactions •Severe infusion reactions have occurred in patients in clinical trials of TECENTRIQ. Infusion-related reactions occurred in 1.7% of patients in UC, and 1.6% in NSCLC •Interrupt or slow the rate of infusion in patients with Grade 2 infusion-related reactions. Permanently discontinue TECENTRIQ in patients with Grade 3 or 4 infusion reactions Embryo-Fetal Toxicity •Based on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman. Advise pregnant women or women planning to become pregnant of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECENTRIQ and for at least 5 months after the last dose of TECENTRIQ Nursing Mothers •Because of the potential for serious adverse reactions in breastfed infants from TECENTRIQ, advise female patients not to breastfeed while taking TECENTRIQ and for at least 5 months after the last dose Most Common Adverse Reactions The most common adverse reactions in UC (rate ≥20%) included fatigue (52%), decreased appetite (26%), nausea (25%), urinary tract infection (22%), pyrexia (21%), and constipation (21%). The most common adverse reactions in NSCLC (rate ≥20%) included fatigue (46%), decreased appetite (35%), dyspnea (32%), cough (30%), nausea (22%), musculoskeletal pain (22%), and constipation (20%). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6fa682c9-a312-4932-9831-f286908660ee