卡瑞丽珠单抗在肺癌患者中的临床研究进展
Clinical Research Progress of Carrilizumab in Patients with Lung Cancer
DOI: 10.12677/ACM.2022.12121756, PDF,   
作者: 成 伟：潍坊医学院，山东 潍坊；寿光市人民医院，山东 潍坊；高福生*：潍坊医学院，山东 潍坊；潍坊医学院附属医院，山东 潍坊
关键词: 卡瑞利珠单抗；免疫；肺癌；治疗；Carrilizumab； Immunity； Lung Cancer； Treatment
摘要: 卡瑞利珠单抗是一种人源化的IgG4单抗，为程序性死亡受体1 (PD-1)抑制剂，与PD-1受体结合，阻断PD-1/PD-L1的结合，从而有效降低T细胞耗竭，有助于发挥持续抑瘤作用。卡瑞丽珠单抗于2019年5月NMPA获批上市，是目前拥有适应症最多的国产PD-1单抗，目前研究发现对广泛期小细胞肺癌、晚期非鳞状非小细胞肺癌患者及晚期鳞状非小细胞肺癌均有治疗作用，结合药物预测标志物、临床有效性及经济效益指导选择最合适的人群使用卡瑞利珠单抗，从而实现精准治疗，具有重要的意义。
Abstract: Carrelizumab is a humanized IgG4 monoclonal antibody, which is a programmed death receptor 1 (PD-1) inhibitor. It binds to the PD-1 receptor and blocks the binding of PD-1/PD-L1, thus effectively reducing T cell depletion and contributing to the sustainable tumor inhibition. Carrezizumab was approved for market in NMPA in May 2019, and is currently the domestic PD-1 monoclonal anti-body with the most indications. Current studies have found that it has therapeutic effects on pa-tients with extensive small cell lung cancer, advanced non-squamous non-small cell lung cancer and advanced squamous non-small cell lung cancer. Combining drug predictive markers, clinical effec-tiveness and economic benefits, it is of great significance to guide the selection of the most appro-priate population to use carrilizumab, so as to achieve precise treatment.
文章引用：成伟, 高福生. 卡瑞丽珠单抗在肺癌患者中的临床研究进展[J]. 临床医学进展, 2022, 12(12): 12191-12197. https://doi.org/10.12677/ACM.2022.12121756

参考文献

[1] Markham, A. and Keam, S.J. (2019) Camrelizumab: First Global Approval. Drugs, 79, 1355-1361. [Google Scholar] [CrossRef] [PubMed]
[2] Wang, J.T., Su, S., Li, J., et al. (2021) Efficacy and Safety of Camrelizumab Monotherapy and Combination Therapy for Cancers: A Systematic Review and Meta-Analysis. Frontiers in Oncology, 11, Article ID: 695512. [Google Scholar] [CrossRef] [PubMed]
[3] Wei, Z., Yang, X., Ye, X., et al. (2019) Camrelizumab Combined with Microwave Ablation Improves the Objective Response Rate in Advanced Non-Small Cell Lung Cancer. Journal of Cancer Research and Erapeutics, 15, 1629-1634. [Google Scholar] [CrossRef] 
[4] 中国临床肿瘤学会抗肿瘤药物安全管理专家委员会, 中国临床肿瘤学会免疫治疗专家委员会. 卡瑞利珠单抗致反应性皮肤毛细血管增生症临床诊治专家共识[J]. 临床肿瘤学杂志, 2020, 25(9): 840-848.
[5] Xing, P.Y., Wang, M.Z., Zhao, J., et al. (2021) Study Protocol: A Single-Arm, Mul-ticenter, Phase II Trial of Camrelizumab plus Apatinib for Advanced Nonsquamous NSCLC Previously Treated with First-Line Immunotherapy. Thoracic Cancer, 12, 2825-2828. [Google Scholar] [CrossRef] [PubMed]
[6] Qin, S., Ren, Z., Meng, Z., et al. (2020) Camrelizumab in Patients with Previously Treated Advanced Hepatocellular Carci-noma: A Multicentre, Open-Label, Parallel-Group, Randomised, Phase 2 Trial. The Lancet Oncology, 21, 571-580. [Google Scholar] [CrossRef] 
[7] Zhou, C., Wu, L., Fan, Y., et al. (2021) Sintilimab plus Plat-inum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results from a Random-ized, Double-Blind, Phase 3 Trial (ORIENT-12). Journal of Thoracic Oncology, 16, 1501-1511. [Google Scholar] [CrossRef] [PubMed]
[8] Behera, M., Ragin, C., Kim, S., et al. (2016) Trends, Predictors, and Impact of Systemic Chemotherapy in Small Cell Lung Cancer Patients between 1985 and 2005. Cancer, 122, 50-60. [Google Scholar] [CrossRef] [PubMed]
[9] Chen, W., Zheng, R., Baade, P.D., et al. (2016) Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 66, 115-132. [Google Scholar] [CrossRef] [PubMed]
[10] Hanna, N., Johnson, D., Temin, S., et al. (2017) Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update Summary. Journal of Oncology Practice, 13, 832-837. [Google Scholar] [CrossRef] 
[11] Zhou, H.Y., Lin, L.L. and Qin, T., et al. (2021) Neoadjuvant Camrelizumab, Nab-Paclitaxel, and Carboplatin in Patients with Stage IB-IIIA Non-Small Cell Lung Cancer (NANE-LC): A Study Protocol of Prospective, Single-Arm, Multicenter, Phase II Study. Journal of Thoracic Disease, 13, 6468-6475. [Google Scholar] [CrossRef] [PubMed]
[12] Zhou, C.C., Chen, G., Huang, Y., et al. (2021) Camrelizumab plus Car-boplatin and Pemetrexed versus Chemotherapy Alone in Chemotherapy-Naive Patients with Advanced Non-Squamous Non-Small-Cell Lung Cancer (CameL): A Randomised, Open-Label, Multicentre, Phase 3 Trial. The Lancet Respiratory Medicine, 9, 305-314. [Google Scholar] [CrossRef] 
[13] Socinski, M.A., Obasaju, C., Gandara, D., et al. (2018) Cur-rent and Emergent Therapy Options for Advanced Squamous Cell Lung Cancer. Journal of Thoracic Oncology, 13, 165-183. [Google Scholar] [CrossRef] [PubMed]
[14] Satpathy, S., Krug, K., Jean Beltran, P.M., et al. (2021) A Proteogenomic Portrait of Lung Squamous Cell Carcinoma. Cell, 184, 4348-4371.
[15] The Cancer Genome Atlas Re-search Network (2012) Comprehensive Genomic Characterization of Squamous Cell Lung Cancers. Nature, 489, 519-525. [Google Scholar] [CrossRef] [PubMed]
[16] Grant, M.J., Herbst, R.S. and Goldberg, S.B. (2021) Selecting the Optimal Immunotherapy Regimen in Driver-Negative Metastatic NSCLC. Nature Reviews Clinical Oncology, 18, 625-644. [Google Scholar] [CrossRef] [PubMed]
[17] Wang, M., Herbst, R.S. and Boshof, C. (2021) Toward Person-alized Treatment Approaches for Non-Small-Cell Lung Cancer. Nature Medicine, 27, 1345-1356. [Google Scholar] [CrossRef] [PubMed]
[18] Paz-Ares, L., Luft, A., Vicente, D., et al. (2018) Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. New England Journal of Medicine, 379, 2040-2051. [Google Scholar] [CrossRef] 
[19] Paz-Ares, L., Vicente, D., Tafreshi, A., Robinson, A., et al. (2020) A Randomized, Placebo-Controlled Trial of Pembrolizumab plus Chemotherapy in Patients with Metastatic Squamous NSCLC: Protocol Specified Final Analysis of KEYNOTE-407. Journal of Thoracic Oncology, 15, 1657-1669. [Google Scholar] [CrossRef] [PubMed]
[20] Wang, J., Lu, S., Yu, X., et al. (2021) Tislelizumab plus Chemo-therapy vs Chemotherapy Alone as First-Line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncology, 7, 709-717. [Google Scholar] [CrossRef] [PubMed]
[21] Jiang, W., Guan, R.T., Shao, Y.W., et al. (2020) Clinical Benefit from a Combination of Brigatinib and Camrelizumab in Sar-comatoid Transformation of ALK-Rearranged Squamous Cell Lung Cancer Resistant to Crizotinib. JTO Clinical and Re-search Reports, 1, Article ID: 100009. [Google Scholar] [CrossRef] [PubMed]
[22] Bray, F., Ferlay, J., Soerjomataram, I., et al. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. [Google Scholar] [CrossRef] [PubMed]
[23] Remon, J., Aldea, M., Besse, B., et al. (2021) Small Cell Lung Cancer: A Slightly Less Orphan Disease after Immunotherapy. Annals of Oncology, 32, 698-709. [Google Scholar] [CrossRef] [PubMed]
[24] George, J., Lim, J.S., Jang, S.J., et al. (2015) Comprehensive Genomic Profiles of Small Cell Lung Cancer. Nature, 524, 47-53.
[25] Govindan, R., Page, N., Morgensztern, D., et al. (2006) Changing Epidemiology of Small-Cell Lung Cancer in the United States over the Last 30 Years: Analysis of the Surveillance, Epidemiologic, and End Results Database. Journal of Clinical Oncology, 24, 4539-4544. [Google Scholar] [CrossRef] 
[26] Amarasena, I.U., Chatterjee, S., Walters, J.A., et al. (2015) Plati-num versus Non-Platinum Chemotherapy Regimens for Small Cell Lung Cancer. Cochrane Database of Systematic Re-views, No. 8, Cd006849. [Google Scholar] [CrossRef] 
[27] Tariq, S., Kim, S.Y., Novaes, J.M.D. and Cheng, H.Y. (2021) Update 2021: Management of Small Cell Lung Cancer. Lung, 199, 579-587. [Google Scholar] [CrossRef] [PubMed]
[28] Fan, Y., Zhao, J., Wang, Q., et al. (2020) Camrelizumab plus Apatinib in Extensive-Stage SCLC (PASSION): A Multicenter, Two-Stage, Phase 2 Trial. Journal of Thoracic Oncolo-gy, 6, 299-309.
[29] Atel, S.P. (2015) PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Molecu-lar Cancer Therapeutics, 14, 847-856. [Google Scholar] [CrossRef] 
[30] Aguilar, E.J., Ric-ciuti, B., Gainor, J., et al. (2019) Outcomes to First-Line Pembrolizumab in Patients with Non-Small Cell Lung Cancer and a PD-L1 Tumor Proportion Score ≥ 90%. Journal of Clinical Oncology, 37, 503. [Google Scholar] [CrossRef] 
[31] Chen, Y., Liu, Q., Chen, Z., et al. (2019) PD-L1 Expres-sion and Tumor Mutational Burden Status for Prediction of Response to Chemotherapy and Targeted Therapy in Non-Small Cell Lung Cancer. Journal of Experimental & Clinical Cancer Research, 38, 193. [Google Scholar] [CrossRef] [PubMed]
[32] Trefny, M.P., Rothschild, S.I., Uhlenbrock, F., et al. (2019) A Variant of a Killer Cell Immunoglobulin-Like Receptor Is Associated with Resistance to PD-1 Blockade in Lung Cancer. Clinical Cancer Research, 25, 3026-3034. [Google Scholar] [CrossRef] 
[33] Mazzaschi, G., Madeddu, D., Falco, A., et al. (2018) Low PD-1 Expression in Cytotoxic CD8 Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvi-ronment in NSCLC with a Prognostic and Predictive Value. Clinical Cancer Research, 24, 407-419. [Google Scholar] [CrossRef] 
[34] Pitt, J.M., Wetizou, M., Daillere, R., et al. (2016) Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors. Immunity, 44, 1255-1269. [Google Scholar] [CrossRef] [PubMed]
[35] Pabla, S., Conroy, J.M., Nesline, M.K., et al. (2019) Proliferative Potential and Resistance to Immune Checkpoint Blockade in Lung Cancer Patients. The Journal for Immu-noTherapy of Cancer, 7, 27. [Google Scholar] [CrossRef] [PubMed]
[36] Jiang, T., Chen, J.H., Xu, X.X., et al. (2022) On-Treatment Blood TMB as Predictors for Camrelizumab plus Chemotherapy in Advanced Lung Squamous Cell Carcinoma: Biomarker Analysis of a Phase III Trial. Molecular Cancer, 21, 4. [Google Scholar] [CrossRef] [PubMed]
[37] Chen, Y., Li, X.B., Liu, G.F., et al. (2020) ctDNA Concentration, MIKI67 Mutations and Hyper-Progressive Disease Related Gene Mutations Are Prognostic Markers for Camrelizumab and Apatinib Combined Multiline Treatment in Advanced NSCLC. Frontiers in Oncology, 10, 1706. [Google Scholar] [CrossRef] [PubMed]
[38] Wang, Y.H., Shi, X.H., Qi, Q.H., et al. (2021) Safety of Anlotinib Capsules Combined with PD-1 Inhibitor Camrelizumab in the Third-Line Treatment of Advanced Non-Small-Cell Lung Cancer and Their Effect on Serum Tumor Markers. Journal of Healthcare Engineering, 2021, Article ID: 2338800. [Google Scholar] [CrossRef] [PubMed]
[39] Liu, Q., Zhou, Z., Zeng, X.H., et al. (2021) Cost-Effectiveness of Domestic PD-1 Inhibitor Camrelizumab Combined with Chemotherapy in the First-Line Treatment of Advanced Nonsquamous Non-Small-Cell Lung Cancer in China. Frontiers in Pharmacology, 12, Article ID: 728440. [Google Scholar] [CrossRef] [PubMed]
[40] Chen, Z., Xing, X.-X., Wu, B., et al. (2021) Cost-Effectiveness Analysis of Camrelizumab plus Chemotherapy vs. Chemotherapy Alone as the First-Line Treatment in Patients with IIIB-IVNon-Squamous Non-Small Cell Lung Cancer (NSCLC) without EGFR and ALK Alteration from a Perspective of Healthcare System in China. Frontiers in Pharmacology, 12, Article ID: 735536. [Google Scholar] [CrossRef] [PubMed]
[41] Xiang, G.Y., Gu, L.N., Chen, X., et al. (2021) Economic Evalua-tion of First-Line Camrelizumab for Advanced Non-Small-Cell Lung Cancer in China. Frontiers in Public Health, 9, Ar-ticle ID: 743558. [Google Scholar] [CrossRef] [PubMed]

为你推荐