PD-1抑制剂纳武利尤单抗的药理作用与临床评价
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摘要
纳武利尤单抗(nivolumab),是一种针对程序性死亡蛋白1(programmed death 1,PD-1)受体的人源化单克隆抗体(IgG4亚型)。本品单药适用于治疗表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变阴性和间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)阴性、既往接受过含铂方案化疗后疾病进展或不可耐受的局部晚期或转移性非小细胞肺癌(non-small cell lung cancer,NSCLC)的成人患者。纳武利尤单抗作为首个PD-1单抗于2018年6月在中国批准上市,是目前唯一用于肺癌治疗的PD-1抑制剂,获批的肿瘤类型为非小细胞肺癌,本文对其药理作用、药动学、临床评价、安全性和药物相互作用进行综述。
Nivolumab,a humanized monoclonal antibody( IgG4 subtype),targets the programmed death 1( PD-1) receptor. This single drug is suitable for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer( NSCLC) who have negative mutation of epidermal growth factor receptor( EGFR) gene and negative anaplastic lymphoma kinase( ALK),and who have previously undergone platinum-containing chemotherapy for disease progression or intolerance. As the first PD-1 monoclonal antibody approved in China in June,2018,nivolumab monoclonal antibody is the only one PD-1 blocking antibody currently approved for non-small cell lung cancer( NSCLC). This article reviews the pharmacological effects,pharmacokinetics,clinical evaluation,safety and drug interactions of nivolumab.
Nivolumab,a humanized monoclonal antibody( IgG4 subtype),targets the programmed death 1( PD-1) receptor. This single drug is suitable for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer( NSCLC) who have negative mutation of epidermal growth factor receptor( EGFR) gene and negative anaplastic lymphoma kinase( ALK),and who have previously undergone platinum-containing chemotherapy for disease progression or intolerance. As the first PD-1 monoclonal antibody approved in China in June,2018,nivolumab monoclonal antibody is the only one PD-1 blocking antibody currently approved for non-small cell lung cancer( NSCLC). This article reviews the pharmacological effects,pharmacokinetics,clinical evaluation,safety and drug interactions of nivolumab.
引文
[1] SHI T,MA YY,YU LF,et al. Cancer immunotherapy:a focus on the regulation of immune checkpoints[J]. Int J Mol Sci,2018,19(5):1389.
[2] BRAHMER J,RECKAMP KL,BAAS P,et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer[J]. N Engl J Med,2015,373(2):123-135.
[3] RIZVI NA,MAZIRES J,PLANCHARD D,et al. Activity and safety of nivolumab,an anti-PD-1 immune checkpoint inhibitor,for patients with advanced,refractory squamous non-small-cell lung cancer(CheckMate 063):a phase 2,single-arm trial[J].Lancet Oncol,2015,16(3):257-265.
[4] GETTINGER SN,HORN L,GANDHI L,et al. Overall survival and long-term safety of nivolumab(anti-programmed death 1 antibody,bms-936558,ono-4538)in patients with previously treated advanced non-small-cell lung cancer[J]. J Clin Oncol,2015,33(18):2004-2012.
[5] HORN L,SPIGEL DR,VOKES EE,et al. Nivolumab versus docetaxel in previously treated patients with advanced non-smallcell lung cancer:two-year outcomes from two randomized,openlabel,phase iii trials(checkmate 017 and checkmate 057)[J].J Clin Oncol,2017,35(35):3924-3933.
[6] GEORGE S,MOTZER RJ,HAMMERS HJ,et al. Safety and efficacy of nivolumab in patients with metastatic renal cell carcinoma treated beyond progression:a subgroup analysis of a randomized clinical trial[J]. JAMA Oncol,2016,2(9):1179-1186.
[7] WU YL,LU S,CHENG Y,et al. Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced NSCLC:CheckMate 078 randomized phase III clinical trial[J]. J Thorac Oncol,2019,14(5):867-875.
[8] BRUSTUGUN OT,SPRAUTEN M,HELLAND. Real-world data on nivolumab treatment of non-small cell lung cancer[J].Acta Oncol,2017,56(3):438-440.
[9] KRIEG C,NOWICKA M,GUGLIETTA S,et al. High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy[J]. Nat Med,2018,24(2):144-153.
[10] KANG YK,BOKU N,SATOH T,et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to,or intolerant of,at least two previous chemotherapy regimens(ONO-4538-12, ATTRACTION-2):a randomised,double-blind,placebo-controlled, phase 3 trial[J]. Lancet,2017,390(10111):2461-2471.
[11] FUJIMOTO D,MORIMOTO T,ITO J,et al. A pilot trial of nivolumab treatment for advanced non-small cell lung cancer patients with mild idiopathic interstitial pneumonia[J]. Lung Cancer,2017,111:1-5.
[12] DUMENIL C,MASSIANI MA,DUMOULIN J,et al. Clinical factors associated with early progression and grade 3-4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab[J]. PLoS One,2018,13(4):e0195945.
[13] KANDA S,GOTO K,SHIRAISHI H,et al. Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer:a four arms phase Ib study.[J]. Ann Oncol,2016,27(12):2242-2250.
[14] CHAMPIAT S,DERCLE L,AMMARI S,et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1[J]. Clin Cancer Res,2017,23(8):1920-1928.
[15]汪龙,张莉,程军,等. Nivolumab致免疫相关性肺炎文献分析[J].中国新药杂志,2019,28(2):252-256.
[16]从俊杰,宿央央,霍春芳,等. PD-1/PD-L1抗体的专利分析[J].今日药学,2017,27(6):420-424.
[17] WEBER J,MANDALA M,DEL VECCHIO M,et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma[J]. N Engl J Med,2017,377(19):1824-1835.
[18] KAZANDJIAN D,KHOZIN S,BLUMENTHAL G,et al. Benefit-risk summary of nivolumab for patients with metastatic squamous cell lung cancer after platinum-based chemotherapy:a report from the us food and drug administration[J]. JAMA Oncol,2016,2(1):118-122.
[19] ISHIHARA H,KONDO T,TAKAGI T,et al. Immediate progressive disease in patients with metastatic renal cell carcinoma treated with nivolumab:a multi-institution retrospective study[J]. Target Oncol,2018,13(5):611-619.
[20] HERBAUX C,GAUTHIER J,BRICE P,et al. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma[J]. Blood,2017,129(18):2471-2478.
[21] OVERMAN MJ,MCDERMOTT R,LEACH JL,et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer(CheckMate142):an open-label,multicentre,phase 2 study[J]. Lancet Oncol,2017,18(9):1182-1191.
[22] FINKELMEIER F,WAIDMANN O,TROJAN J. Nivolumab for the treatment of hepatocellular carcinoma[J]. Expert Rev Anticancer Ther,2018,18(12):1169-1175.
[2] BRAHMER J,RECKAMP KL,BAAS P,et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer[J]. N Engl J Med,2015,373(2):123-135.
[3] RIZVI NA,MAZIRES J,PLANCHARD D,et al. Activity and safety of nivolumab,an anti-PD-1 immune checkpoint inhibitor,for patients with advanced,refractory squamous non-small-cell lung cancer(CheckMate 063):a phase 2,single-arm trial[J].Lancet Oncol,2015,16(3):257-265.
[4] GETTINGER SN,HORN L,GANDHI L,et al. Overall survival and long-term safety of nivolumab(anti-programmed death 1 antibody,bms-936558,ono-4538)in patients with previously treated advanced non-small-cell lung cancer[J]. J Clin Oncol,2015,33(18):2004-2012.
[5] HORN L,SPIGEL DR,VOKES EE,et al. Nivolumab versus docetaxel in previously treated patients with advanced non-smallcell lung cancer:two-year outcomes from two randomized,openlabel,phase iii trials(checkmate 017 and checkmate 057)[J].J Clin Oncol,2017,35(35):3924-3933.
[6] GEORGE S,MOTZER RJ,HAMMERS HJ,et al. Safety and efficacy of nivolumab in patients with metastatic renal cell carcinoma treated beyond progression:a subgroup analysis of a randomized clinical trial[J]. JAMA Oncol,2016,2(9):1179-1186.
[7] WU YL,LU S,CHENG Y,et al. Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced NSCLC:CheckMate 078 randomized phase III clinical trial[J]. J Thorac Oncol,2019,14(5):867-875.
[8] BRUSTUGUN OT,SPRAUTEN M,HELLAND. Real-world data on nivolumab treatment of non-small cell lung cancer[J].Acta Oncol,2017,56(3):438-440.
[9] KRIEG C,NOWICKA M,GUGLIETTA S,et al. High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy[J]. Nat Med,2018,24(2):144-153.
[10] KANG YK,BOKU N,SATOH T,et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to,or intolerant of,at least two previous chemotherapy regimens(ONO-4538-12, ATTRACTION-2):a randomised,double-blind,placebo-controlled, phase 3 trial[J]. Lancet,2017,390(10111):2461-2471.
[11] FUJIMOTO D,MORIMOTO T,ITO J,et al. A pilot trial of nivolumab treatment for advanced non-small cell lung cancer patients with mild idiopathic interstitial pneumonia[J]. Lung Cancer,2017,111:1-5.
[12] DUMENIL C,MASSIANI MA,DUMOULIN J,et al. Clinical factors associated with early progression and grade 3-4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab[J]. PLoS One,2018,13(4):e0195945.
[13] KANDA S,GOTO K,SHIRAISHI H,et al. Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer:a four arms phase Ib study.[J]. Ann Oncol,2016,27(12):2242-2250.
[14] CHAMPIAT S,DERCLE L,AMMARI S,et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1[J]. Clin Cancer Res,2017,23(8):1920-1928.
[15]汪龙,张莉,程军,等. Nivolumab致免疫相关性肺炎文献分析[J].中国新药杂志,2019,28(2):252-256.
[16]从俊杰,宿央央,霍春芳,等. PD-1/PD-L1抗体的专利分析[J].今日药学,2017,27(6):420-424.
[17] WEBER J,MANDALA M,DEL VECCHIO M,et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma[J]. N Engl J Med,2017,377(19):1824-1835.
[18] KAZANDJIAN D,KHOZIN S,BLUMENTHAL G,et al. Benefit-risk summary of nivolumab for patients with metastatic squamous cell lung cancer after platinum-based chemotherapy:a report from the us food and drug administration[J]. JAMA Oncol,2016,2(1):118-122.
[19] ISHIHARA H,KONDO T,TAKAGI T,et al. Immediate progressive disease in patients with metastatic renal cell carcinoma treated with nivolumab:a multi-institution retrospective study[J]. Target Oncol,2018,13(5):611-619.
[20] HERBAUX C,GAUTHIER J,BRICE P,et al. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma[J]. Blood,2017,129(18):2471-2478.
[21] OVERMAN MJ,MCDERMOTT R,LEACH JL,et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer(CheckMate142):an open-label,multicentre,phase 2 study[J]. Lancet Oncol,2017,18(9):1182-1191.
[22] FINKELMEIER F,WAIDMANN O,TROJAN J. Nivolumab for the treatment of hepatocellular carcinoma[J]. Expert Rev Anticancer Ther,2018,18(12):1169-1175.