化疗联合免疫治疗非小细胞肺癌的最新研究进展
Recent Advances in Chemotherapy Combined with Immunotherapy for Non-Small Cell Lung Cancer
DOI: 10.12677/ACM.2023.1381907, PDF,   
作者: 邓隽军*, 陈丹蕾：青海大学临床医学院，青海 西宁；赵大勇：郑州大学第一附属医院肿瘤外科，河南 郑州；李 淼：青海省第五人民医院肿瘤内科，青海 西宁
关键词: 非小细胞肺癌；化疗联合免疫治疗；研究进展；Non-Small Cell Lung Cancer； Chemotherapy Combined with Immunotherapy； Research Progress
摘要: 肺癌是发病率及死亡率极高的恶性肿瘤，其中非小细胞肺癌占80%~85%，化疗是非小细胞肺癌治疗的基石，但随着疾病的进展，单一的化疗疗效也不尽人意，免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)是目前非小细胞肺癌(non-small cell lung cancer, NSCLC)的研究热点，近年来发展迅速，但单药治疗获益人群仍有限，近年来一系列化疗联合免疫治疗试验在临床治疗中取得了巨大进展，鉴于此，本综述旨在概括化疗联合免疫治疗非小细胞肺癌的最新研究进展。
Abstract: Lung cancer is a malignant tumor with extremely high incidence and mortality, among which non-small cell lung cancer accounts for 80%~85%. Chemotherapy is the cornerstone of treatment for non-small cell lung cancer. However, with the progression of the disease, the efficacy of single chemotherapy is not satisfactory. Immune checkpoint inhibitors (ICIs) are currently the focus of research in non-small cell lung cancer (NSCLC), which have developed rapidly in recent years, but the population benefiting from monotherapy is still limited. In recent years, a series of chemother-apy combined immunotherapy trials have made great progress in clinical treatment. In view of this, this review aims to summarize the latest research progress of chemotherapy combined immuno-therapy in non-small cell lung cancer.
文章引用：邓隽军, 陈丹蕾, 赵大勇, 李淼. 化疗联合免疫治疗非小细胞肺癌的最新研究进展[J]. 临床医学进展, 2023, 13(8): 13645-13653. https://doi.org/10.12677/ACM.2023.1381907

参考文献

[1] Zhang, S., Sun, K., Zheng, R., et al. (2021) Cancer Incidence and Mortality in China, 2015. Journal of the National Cancer Center, 1, 2-11. [Google Scholar] [CrossRef] [PubMed]
[2] Chen, P., Liu, Y., Wen, Y. and Zhou, C. (2022) Non-Small Cell Lung Cancer in China. Cancer Communications, 42, 937-970. [Google Scholar] [CrossRef] [PubMed]
[3] Hoy, H., Lynch, T. and Beck, M. (2019) Surgical Treatment of Lung Can-cer. Critical Care Nursing Clinics of North America, 31, 303-313. [Google Scholar] [CrossRef] [PubMed]
[4] Jones, G.S. and Baldwin, D.R. (2018) Recent Advances in the Management of Lung Cancer. Clinical Medicine Journal, 18, s41-s46. [Google Scholar] [CrossRef] [PubMed]
[5] Felip, E., Altorki, N., Zhou, C., et al. (. 2021) Adjuvant Ate-zolizumab after Adjuvant Chemotherapy in Resected Stage IB-IIIA Non-Small-Cell Lung Cancer [IMpower010]: A Randomised, Multicentre, Open-Label, Phase 3 Trial. Lancet, 398, 1344-1357. [Google Scholar] [CrossRef] 
[6] Langer, C.J., Gadgeel, S.M., Borghaei, H., et al. (2016) Carboplatin and Pemetrexed with or without Pembrolizumab for Advanced, Non-Squamous Non-Small-Cell Lung Can-cer: A Randomised, Phase 2 Cohort of the Open-Label KEYNOTE-021 Study. The Lancet Oncology, 17, 1497-1508. [Google Scholar] [CrossRef] 
[7] Gandhi, L., Rodriguez-Abreu, D., Gadgeel, S., et al. (2018) Pembroli-Zumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. New England Journal of Medicine, 378, 2078-2092. [Google Scholar] [CrossRef] 
[8] Yan, N., Huang, S., Li, L., et al. (2022) Case Report: Durable Re-sponse to Immuno-Chemotherapy in a Case of ROS1 Fusion-Positive Advanced Lung Adenocarcinoma: A Case Report. Frontiers in Pharmacology, 13, Article 898623. [Google Scholar] [CrossRef] [PubMed]
[9] Chen, M., Xu, Y., Zhao, J., et al. (2023) Comparison of Chemo-therapy plus Pembrolizumab vs. Chemotherapy Alone in EGFR-Mutant Non-Small-Cell Lung Cancer Patients. Clinical Lung Cancer, 24, 278-286. [Google Scholar] [CrossRef] [PubMed]
[10] Carbone, D.P., Reck, M., Paz-Ares, L., et al. (2017) First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. New England Journal of Medicine, 376, 2415-2426. [Google Scholar] [CrossRef] 
[11] Darrason, M., Chatelain, E., Ranchon, F., et al. (2020) Do Systemic Treatments Delivered after Nivolumab Result in Better Outcomes? A Bicentric Case-Control Study. Respiratory Medicine and Research, 77, 100-105. [Google Scholar] [CrossRef] [PubMed]
[12] Brahmer, J.R., Lee, J.S., Ciuleanu, T.E., et al. (2023) Five-Year Survival Outcomes with Nivolumab plus Ipilimumab versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227. Journal of Clinical Oncology, 41, 1200-1212. [Google Scholar] [CrossRef] 
[13] Paz-Ares, L., Ciuleanu, T.E., Cobo, M., et al. (2021) First-Line Nivolumab plus Ipilimumab Combined with Two Cycles of Chemotherapy in Patients with Non-Small-Cell Lung Cancer (CheckMate 9LA): An International, Randomised, Open-Label, Phase 3 Trial. The Lancet Oncology, 22, 198-211. [Google Scholar] [CrossRef] 
[14] Paz-Ares, L.G., Ciuleanu, T.E., Pluzanski, A., et al. (2023) Safety of First-Line Nivolumab plus Ipilimumab in Patients with Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Journal of Thoracic Oncology, 18, 79-92. [Google Scholar] [CrossRef] [PubMed]
[15] Xu, N., Ying, K., Wang, Z., et al. (2019) Phase Ib Study of Sintili-mab in Combination with Chemotherapy for 1L Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC). Journal of Clinical Oncology, 37, e20546. [Google Scholar] [CrossRef] 
[16] Yang, Y., Wang, Z.., Fang, J., et al. (2020) Efficacy and Safety of Sintilimab plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: A Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT An-ti-PD-1-11). Journal of Thoracic Oncology, 15, 1636-1646. [Google Scholar] [CrossRef] [PubMed]
[17] Jiang, H., Zheng, Y., Qian, J., et al. (2021) Efficacy and Safety of Sintilimab in Combination with Chemotherapy in Previously Untreated Advanced or Metastatic Nonsquamous or Squa-mous NSCLC: Two Cohorts of an Open-Label, Phase 1b Study. Cancer Immunology, Immunotherapy, 70, 857-868. [Google Scholar] [CrossRef] [PubMed]
[18] Molife, C., Brnabic, A., Stefaniak, V.J., et al. (2023) Sintilimab plus Chemotherapy for First-Line Treatment of Advanced or Metastatic Nonsquamous Non-Small-Cell Lung Cancer: Network Meta-Analysis. Immunotherapy, 15, 293-309. [Google Scholar] [CrossRef] [PubMed]
[19] Lee, A. and Keam, S.J. (2020) Tislelizumab: First Approval. Drugs, 80, 617-624. [Google Scholar] [CrossRef] [PubMed]
[20] Dahan, R., Sega, E., Engelhardt, J., et al. (2015) FcγRs Modulate the Anti-Tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis. Cancer Cell, 28, 285-295. [Google Scholar] [CrossRef] [PubMed]
[21] Shen, L., Guo, J., Zhang, Q., et al. (2020) Tislelizumab in Chinese Patients with Advanced Solid Tumors: An Open-Label, Non-Comparative, Phase 1/2 Study. Journal for ImmunoThera-py of Cancer, 8, e000437corr1. [Google Scholar] [CrossRef] [PubMed]
[22] Wang, Z., Zhao, J., Ma, Z., Cui, J., et al. (2020) A Phase 2 Study of Tislelizumab in Combination with Platinum-Based Chemotherapy as First-line Treatment for Advanced Lung Cancer in Chinese Patients. Lung Cancer, 147, 259-268. [Google Scholar] [CrossRef] [PubMed]
[23] Lu, S., Wang, J., Yu, Y., et al. (2021) Tislelizumab plus Chemotherapy as First-Line Treatment for Locally Advanced or Meta-static Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. Journal of Thoracic Oncology, 16, 1512-1522. [Google Scholar] [CrossRef] [PubMed]
[24] Wang, J., Lu, S., Yu, X., et al. (2021) Tislelizumab plus Chemotherapy 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]
[25] Zhu, W., Geng, Q., Peng, H., et al. (2022) Efficacy and Safety of Low-Dose Nab-Paclitaxel plus Tislelizumab in Elderly Patients with Previously Treated Metastatic Non-Small Cell Lung Cancer. Frontiers in Oncology, 12, Article 802467. [Google Scholar] [CrossRef] [PubMed]
[26] Lu, S., Yu, Y., Barnes, G., Qiu, X., et al. (2022) Examining the Impact of Tislelizumab Added to Chemotherapy on Health-Related Quality-of-Life Outcomes in Previously Untreated Patients with Nonsquamous Non-Small Cell Lung Cancer. The Cancer Journal, 28, 96-104. [Google Scholar] [CrossRef] 
[27] Jiang, T., Wang, P., Zhang, J., et al. (2021) Toripalimab plus Chemotherapy as Second-Line Treatment in Previously EGFR-TKI Treated Patients with EGFR-Mutant-Advanced NSCLC: A Multicenter Phase-II Trial. Signal Transduction and Targeted Ther-apy, 6, Article No. 355. [Google Scholar] [CrossRef] [PubMed]
[28] Zhou, J., Zhou, F., Xie, H., et al. (2020) An Advanced Non-Small Cell Lung Cancer Patient with Epidermal Growth Factor Receptor Sensitizing Mutation Re-sponded to Toripalimab in Combination with Chemotherapy after Resistance to Osimertinib: A Case Report. Transla-tional Lung Cancer Research, 9, 354-359. [Google Scholar] [CrossRef] [PubMed]
[29] Wang, Z., Wu, L., Li, B., et al. (2023) Toripalimab plus Chemothera-py for Patients with Treatment-Naive Advanced Non-Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01). Journal of Clinical Oncology, 41, 651-663. [Google Scholar] [CrossRef] 
[30] Zhou, C., Wang, Z., Sun, Y., et al. (2022) Sugemalimab Versus Placebo, in Combination with Platinum-Based Chemotherapy, as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (GEMSTONE-302): Interim and Final Analyses of a Double-Blind, Randomised, Phase 3 Clinical Trial. The Lancet Oncology, 23, 220-233. [Google Scholar] [CrossRef] 
[31] Chen, P., Li, Y., Jing, X., et al. (2022) Cost-Effectiveness Analysis of Sugemalimab in Combination with Chemotherapy as First-Line Treatment in Chinese Patients with Metastatic NSCLC. Lung Cancer, 174, 157-164. [Google Scholar] [CrossRef] [PubMed]
[32] Pu, X., Wang, Q., Liu, L., et al. (2023) Rh-Endostatin plus Camrelizumab and Chemotherapy in First-Line Treatment of Advanced Non-Small Cell Lung Cancer: A Multicenter Retrospective Study. Cancer Medicine, 12, 7724-7733. [Google Scholar] [CrossRef] [PubMed]
[33] Zhou, C., Chen, G., Huang, Y., et al. (2021Mar) 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] 
[34] Ren, S., Chen, J., Xu, X., et al. (2022) Camrelizumab plus Carboplatin and Paclitaxel as First-Line Treatment for Advanced Squamous NSCLC (CameL-Sq): A Phase 3 Trial. Journal of Thoracic Oncology, 17, 544-557. [Google Scholar] [CrossRef] [PubMed]
[35] Lim, S.W. and Ahn, M.J. (2019) Current Status of Immune Checkpoint Inhibitors in Treatment of Non-Small Cell Lung Cancer. The Korean Journal of Internal Medicine, 34, 50-59. [Google Scholar] [CrossRef] [PubMed]
[36] Socinski, M.A., Nishio, M., et al. (2021) IMpower150 Final Overall Survival Analyses for Atezolizumab plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC. Journal of Thoracic Oncology, 16, 1909-1924. [Google Scholar] [CrossRef] [PubMed]
[37] West, H., McCleod, M., Hussein, M., et al. (2019) Atezolizumab in Combination with Carboplatin plus Nab-Paclitaxel Chemo-therapy Compared with Chemotherapy Alone as First-Line Treatment for Metastatic Non-Squamous Non-Small-Cell Lung Cancer (IMpower130): A Multicentre, Randomised, Open-Label, Phase 3 Trial. The Lancet Oncology, 20, 924-937. [Google Scholar] [CrossRef] 
[38] Shu, C.A., Gainor, J.F., Award, M.M., et al. (2020) Neoad-juvant Atezolizumab and Chemotherapy in Patients with Resectable Non-Small-Cell Lung Cancer: An Open-Label, Mul-ticentre, Single-Arm, Phase 2 Trial. The Lancet Oncology, 21, 786-795. [Google Scholar] [CrossRef] 
[39] Ikeuchi, N., Igata, F., Kinoshita, E., et al. (2023) Real-World Efficacy and Safety of Atezolizumab plus Bevacizumab, Paclitaxel and Carboplatin for First-Line Treatment of Japanese Patients with Metastatic Non-Squamous Non-Small Cell Lung Cancer. Anticancer Research, 43, 713-724. [Google Scholar] [CrossRef] [PubMed]
[40] Morgensztern, D., Dols, M.C., Ponce Aix, S., et al. (2021) Nab-Paclitaxel plus Durvalumab in Patients with Previously Treated Advanced Stage Non-Small Cell Lung Cancer (ABOUND.2L+). Frontiers in Oncology, 10, Article 569715. [Google Scholar] [CrossRef] [PubMed]
[41] Antonia, S.J., Villegas, A., Daniel, D., Vicente, D., et al. (2017) Durvalumab after Chemo-Radiotherapy in Stage III Non-Small-Cell Lung Cancer. New England Journal of Medicine, 377, 1919-1929. [Google Scholar] [CrossRef] 
[42] Spigel, D.R., Faivre-Finn, C., Gray, J.E., Vicente, D., et al. (2022) Five-Year Survival Outcomes from the PACIFIC Trial: Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 40, 1301-1311. [Google Scholar] [CrossRef] 
[43] Borghetti, P., Imbrescia, J., Volpi, G., et al. (2022) Chemo-Radiotherapy plus Durvalumab for Loco-Regional Relapse of Resected NSCLC. Radiation Oncology, 17, Article No. 124. [Google Scholar] [CrossRef] [PubMed]
[44] Tanaka, H., Tanzawa, S., Misumi, T., et al. (2022) A Phase Ii Study of S-1 and Cisplatin with Concurrent Thoracic Radiotherapy Followed by Durvalumab for Unresectable, Locally Advanced Non-Small-Cell Lung Cancer in Japan (SAMURAI Study): Primary Analysis. Therapeutic Advances in Medical Oncology, 14. [Google Scholar] [CrossRef] [PubMed]
[45] Paz-Ares, L., Ciuleanu, T.E., Cobo, M., et al. (2021) First-Line Nivolumab plus Ipilimumab Combined with Two Cycles of Chemotherapy in Patients with Non-Small-Cell Lung Cancer (CheckMate 9LA): An International, Randomised, Open-Label, Phase 3 Trial. The Lancet Oncology, 22, 198-211. [Google Scholar] [CrossRef] 
[46] Paz-Ares, L.G., Ramalingam, S.S., Ciuleanu, T.E., et al. (2022) First-Line Nivolumab plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes from the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. Journal of Thoracic Oncology, 17, 289-308. [Google Scholar] [CrossRef] [PubMed]
[47] Meng, L.-F., Huang, J.-F., Luo, P.-H., Huang, S.-X. and Wang, H.-L. (2022) The Efficacy and Safety of Immune Checkpoint Inhibitor plus Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis. Investigational New Drugs, 40, 810-817. [Google Scholar] [CrossRef] [PubMed]
[48] Sumi, T., Sekikawa, M., Nagahisa, Y., et al. (2022) Relation of Overall Tumor Burden with Severe Immune-Related Adverse Events in Nivolumab plus Ipilimumab Treatment for Lung Cancer. Investigational New Drugs, 40, 1315-1321. [Google Scholar] [CrossRef] [PubMed]

为你推荐