免疫检查点抑制剂治疗晚期胃癌的研究进展
Research Progress of Immune Checkpoint Inhibitors in the Treatment of Advanced Gastric Cancer
摘要: 胃癌(gastric cancer, GC)是世界范围内癌症相关死亡原因第三位,其发病率及死亡率均位居全球恶性肿瘤的前五位。多数胃癌患者确诊时往往已进展至中晚期,缺乏有效的治疗手段,预后极差。尽管化疗和靶向治疗在内的内科治疗是目前晚期胃癌(advanced gastric cancer, AGC)的主要治疗手段,但因为胃癌的异质性,化疗和靶向治疗的疗效似乎已经达到平台期。近年来,免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)治疗在部分恶性肿瘤的治疗中取得重大进展,在AGC中,ICIs的疗效也被多项大规模研究进一步证实。本综述探讨了不同ICIs在晚期胃癌中的临床研究进展及近期研究数据。
Abstract: Gastric cancer is the third leading cause of cancer-related deaths worldwide, and its incidence and mortality rates are among the top five malignant tumors in the world. Most patients with gastric cancer have already progressed to the middle and late stages when diagnosed, and lack of effective treatments, resulting in a very poor prognosis. Although medical treatment, including chemother-apy and targeted therapy, is currently the main treatment for advanced gastric cancer, the efficacy of chemotherapy and targeted therapy seems to have reached a plateau because of the heterogene-ity of gastric cancer. In recent years, immune checkpoint inhibitors (ICIs) therapy has made signifi-cant progress in the treatment of some malignant tumors, and the efficacy of ICIs has been further confirmed by several large-scale studies in AGC. This review discusses the progress of clinical stud-ies and recent research data of different ICIs in advanced gastric cancer.
文章引用:王静如, 张恩慧, 曲颜丽. 免疫检查点抑制剂治疗晚期胃癌的研究进展[J]. 临床医学进展, 2023, 13(10): 16191-16197. https://doi.org/10.12677/ACM.2023.13102264

参考文献

[1] Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I. and Jemal, A. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. [Google Scholar] [CrossRef] [PubMed]
[2] Kole, C., Charalampakis, N., Tsakatikas, S., Kouris, N., Papaxoinis, G. and Michalis, V.K. (2022) Immunotherapy for Gastric Cancer: A 2021 Update. Immunother-apy, 14, 41-64. [Google Scholar] [CrossRef] [PubMed]
[3] Kawazoe, A., Shitara, K., Boku, N., Yoshikawa, T. and Terashima, M. (2021) Current Status of Immunotherapy for Advanced Gastric Cancer. Japanese Journal of Clinical Oncology, 51, 20-27. [Google Scholar] [CrossRef] [PubMed]
[4] Zhang, Y., Yang, Y., Chen, Y.R., Lin, W., Chen, X.L. and Liu, J. (2022) PD-L1: Biological Mechanism, Function, and Immunotherapy in Gastric Cancer. Frontiers in Immunology, 13, Article ID: 1060497. [Google Scholar] [CrossRef] [PubMed]
[5] Eliza, H., Alicia, F.C.O., Demetris, P., Rao, S., Ashley, S. and Charalambous, H. (2011) Docetaxel and Irinotecan as Second-Line Therapy for Advanced Oesophagogastriccancer. Eu-ropean Journal of Cancer (Oxford, England : 1990), 47, 1146-1151. [Google Scholar] [CrossRef] [PubMed]
[6] Hironaka, S., Ueda, S., Yasui, H., Nishina, T., Tsuda, M. and Tsumura, T. (2013) Randomized, Open-Label, Phase III Study Comparing Irinotecan with Paclitaxel in Patients with Advanced Gastric Cancer without Severe Peritoneal Metastasis after Failure of Prior Combination Chemotherapy Using Fluoropyrimidine plus Platinum: WJOG 4007 Trial. Journal of Clinical Oncology: Official Journal of the American Soci-ety of Clinical Oncology, 31, 4438-4444. [Google Scholar] [CrossRef
[7] Zhao, Q., Lian, C.H., Huo, Z.B., Li, M., Liu, Y. and Fan, L.Q. (2020) The Efficacy and Safety of Neoadjuvant Chemotherapy on Patients with Advanced Gastric Cancer: A Multicenter Randomized Clinical Trial. Cancer Medicine, 9, 5731-5745. [Google Scholar] [CrossRef] [PubMed]
[8] Tian, Y., Zhao, Q., Li, Y., Fan, L.Q., Zhang, Z.D. and Zhao, X.F. (2021) Efficacy of Neoadjuvant Chemotherapy DOX and XELOX Regimens for Patients with Resectable Gastric or Gastroesophageal Junction Adenocarcinoma. Gastroenterology Re-search and Practice, 2021, Article ID: 5590626. [Google Scholar] [CrossRef] [PubMed]
[9] Yu, Y.Y., Fang, Y., Shen, Z.B., Wang, Y., Yan, M. and Cao, H. (2019) Oxaliplatin plus Capecitabine in the Perioperative Treatment of Lo-cally Advanced Gastric Adenocarcinoma in Combination with D2 Gastrectomy: NEO-CLASSIC Study. The Oncologist, 24, 1311-e989. [Google Scholar] [CrossRef] [PubMed]
[10] Xue, K., Ying, X.J., Bu, Z.D., Wu, A., Li, Z.W. and Tang, L. (2018) Oxaliplatin plus S-1 or Capecitabine as Neoadjuvant or Adjuvant Chemotherapy for Locally Advanced Gastric Cancer with D2 Lymphadenectomy: 5-Year Follow-Up Results of a Phase II-III Randomized Trial. Chinese Journal of Cancer Research, 30, 516-525. [Google Scholar] [CrossRef] [PubMed]
[11] Leowattana, W., Leowattana, P. and Leowattana, T. (2023) Immunotherapy for Advanced Gastric Cancer. World Journal of Methodology, 13, 79-97. [Google Scholar] [CrossRef] [PubMed]
[12] Wang, J.Z., He, Y.D., Zhang, B.W., Lv, H.F., Nie, C.Y. and Chen, B.B. (2022) The Efficacy and Safety of Sintilimab Combined with Nab-Paclitaxel as a Second-Line Treatment for Advanced or Metastatic Gastric Cancer and Gastroesophageal Junction Cancer. Frontiers in Oncology, 12, Article ID: 924149. [Google Scholar] [CrossRef] [PubMed]
[13] Jin, X., Liu, Z.R., Yang, D.X., Yin, K. and Chang, X.S. (2022) Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer. Frontiers in Immunology, 13, Article ID: 948647. [Google Scholar] [CrossRef] [PubMed]
[14] Zhang, L., Mai, W.Q., Jiang, W.Y. and Geng, Q. (2020) Sintili-mab: A Promising Anti-Tumor PD-1 Antibody. Frontiers in Oncology, 10, Article ID: 594558. [Google Scholar] [CrossRef] [PubMed]
[15] Sun, L.T., Zhang, L.Y., Yu, J.R., Zhang, Y., Pang, X. and Ma, C.H. (2020) Clinical Efficacy and Safety of Anti-PD-1/ PD-L1 Inhibitors for the Treatment of Advanced or Metastatic Cancer: A Systematic Review and Meta-Analysis. Scientific Reports, 10, Article No. 2083. [Google Scholar] [CrossRef] [PubMed]
[16] Muro, K., Chung, H.C., Shankaran, V., Geva, R., Catenacci, D. and Gupta, S. (2016) Pembrolizumab for Patients with PD-L1-Positive Advanced Gastric Cancer (KEYNOTE-012): A Multicentre, Open-Label, Phase 1b Trial. The Lancet Oncology, 17, 717-726. [Google Scholar] [CrossRef
[17] Kang, Y.-K., Boku, N., Satoh, T., Ryu, M.-H., Chao, Y. and Kato, K. (2017) 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. The Lancet (London, England), 390, 2461-2471. [Google Scholar] [CrossRef
[18] Zhang, Z., Liu, N. and Sun, M. (2023) Research Progress of Immunotherapy for Gastric Cancer. Technology in Cancer Research & Treatment, 22. [Google Scholar] [CrossRef] [PubMed]
[19] Fuchs, C.S., Doi, T., Jang, R.W., Muro, K., Satoh, T. and Ma-chado, M. (2018) Safety and Efficacy of Pembrolizumab Monotherapy in Patients with Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncology, 4, e180013. [Google Scholar] [CrossRef] [PubMed]
[20] Kexin, L., Zhang, A., Li, X., Zhang, H.T. and Zhao, L.M. (2021) Advances in Clinical Immunotherapy for Gastric Cancer. Biochimica et Biophysica Acta (BBA)—Reviews on Cancer, 1876, Article ID: 188615. [Google Scholar] [CrossRef] [PubMed]
[21] Bang, Y.-J., Ruiz, E.Y., Cutsem, E.V., Lee, K.-W., Wyrwicz, L. and Schenker, M. (2018) Phase III, Randomised Trial of Avelumab versus Physician’s Choice of Chemotherapy as Third-Line Treatment of Patients with Advanced Gastric or Gastro-Oesophageal Junction Cancer: Primary Analysis of JAVELIN Gastric 300. Annals of Oncology: Official Journal of the European Society for Medical Oncology, 29, 2052-2060. [Google Scholar] [CrossRef] [PubMed]
[22] Kon, E. and Benhar, I. (2019) Immune Checkpoint Inhib-itor Combinations: Current Efforts and Important Aspects for Success. Drug Resistance Updates, 45, 13-29.
[23] Davern, M. and Lysaght, J. (2020) Cooperation between Chemotherapy and Immunotherapy in Gas-troesophageal Cancers. Cancer Letters, 495, 89-99. [Google Scholar] [CrossRef] [PubMed]
[24] Burtness, B., Harrington, K.J., Greil, R., Soulières, D., Tahara, M. and Castro Jr., G.D. (2019) Pembrolizumab Alone or with Chemo-therapy versus Cetuximab with Chemotherapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (KEYNOTE-048): A Randomised, Open-Label, Phase 3 Study. The Lancet (London, England), 394, 1915-1928. [Google Scholar] [CrossRef
[25] Hodge, J.W., Garnett, C.T., Farsaci, B., Palena, C., Tsang, K.-Y. and Ferrone, S. (2013) Chemotherapy-Induced Immunogenic Modulation of Tumor Cells Enhances Killing by Cytotoxic T Lymphocytes and Is Distinct from Immunogenic Cell Death. International Journal of Cancer, 133, 624-636. [Google Scholar] [CrossRef] [PubMed]
[26] Li, J.-Y., Chen, Y.-P., Li, Y.-Q., Liu, N. and Ma, J. (2021) Chemotherapeu-tic and Targeted Agents Can Modulate the Tumor Microenvironment and Increase the Efficacy of Immune Checkpoint Blockades. Molecular Cancer, 20, Article No. 27. [Google Scholar] [CrossRef] [PubMed]
[27] Seliger, B. (2019) Combinatorial Approaches with Checkpoint Inhibitors to Enhance Anti-Tumor Immunity. Frontiers in Immunol-ogy, 10, Article No. 999. [Google Scholar] [CrossRef] [PubMed]
[28] Leong, A. and Kim, M. (2020) The An-giopoietin-2 and TIE Pathway as a Therapeutic Target for Enhancing Antiangiogenic Therapy and Immunotherapy in Pa-tients with Advanced Cancer. International Journal of Molecular Sciences, 21, Article No. 8689. [Google Scholar] [CrossRef] [PubMed]
[29] Zhou, S. and Zhang, H. (2020) Synergies of Targeting Angiogenesis and Immune Checkpoints in Cancer: From Mechanism to Clinical Applications. Anti-Cancer Agents in Medicinal Chem-istry, 20, 768-776. [Google Scholar] [CrossRef] [PubMed]
[30] Zhu, N., Weng, S., Wang, J., Chen, J.Q., Yu, L.Z. and Fang, X.F. (2019) Preclinical Rationale and Clinical Efficacy of Antiangiogenic Therapy and Immune Checkpoint Blockade Combination Therapy in Urogenital Tumors. Journal of Cancer Research and Clinical Oncology, 145, 3021-3036. [Google Scholar] [CrossRef] [PubMed]
[31] Bang, Y.-J., Kang, Y.-K., Catenacci, D.V., Muro, K., Fuchs, C.S. and Geva, R. (2019) Pembrolizumab Alone or in Combination with Chemotherapy as First-Line Therapy for Patients with Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: Results from the Phase II Nonrandom-ized KEYNOTE-059 Study. Gastric Cancer, 22, 828-837. [Google Scholar] [CrossRef] [PubMed]
[32] Shitara, K., Cutsem, E.V., Bang, Y.-J., Fuchs, C., Wyrwicz, L. and Lee, K.-W. (2020) Efficacy and Safety of Pembrolizumab or Pembrolizumab plus Chemotherapy vs Chemotherapy Alone for Patients with First-Line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncology, 6, 1571-1580. [Google Scholar] [CrossRef] [PubMed]
[33] Boku, N., Ryu, M.-H., Kato, K., Chung, H.C., Minashi, K. and Lee, K.-W. (2019) Safety and Efficacy of Nivolumab in Combination with S-1/Capecitabine plus Oxaliplatin in Patients with Previously Untreated, Unresectable, Advanced, or Recurrent Gastric/Gastroesophageal Junction Cancer: Interim Results of a Randomized, Phase II Trial (ATTRACTION- 4). Annals of Oncology, 30, 250-258. [Google Scholar] [CrossRef] [PubMed]
[34] Kang, Y.-K., Chen, L.-T., Ryu, M.-H., Oh, D.-Y., Oh, S.C. and Chung, H.C. (2022) Nivolumab plus Chemotherapy versus Placebo plus Chemotherapy in Patients with HER2-Negative, Untreated, Unresectableadvanced or Recurrent Gastric or Gastro-Oesophageal Junction Cancer (ATTRACTION-4): A Randomised, Multicentre, Double-Blind, Placebo- Controlled, Phase 3 Trial. The Lancet Oncology, 23, 234-247. [Google Scholar] [CrossRef
[35] Janjigian, Y.Y., Shitara, K., Moehler, M., Garrido, M., Sal-man, P. and Shen, L. (2021) First-Line Nivolumab plus Chemotherapy versus Chemotherapy Alone for Advanced Gas-tric, Gastro-Oesophageal Junction, and Oesophageal Adenocarcinoma (CheckMate 649): A Randomised, Open-Label, Phase 3 Trial. The Lancet (London, England), 398, 27-40. [Google Scholar] [CrossRef
[36] Chung, H.C., Bang, Y.-J., Fuchs, C.S., Qin, S.-K., Satoh, T. and Shitara, K. (2021) First-Line Pembrolizumab/Placebo plus Trastuzumab and Chemotherapy in HER2-Positive Ad-vanced Gastric Cancer: KEYNOTE-811. Future Oncology (London, England), 17, 491-501. [Google Scholar] [CrossRef] [PubMed]
[37] Xu, J., Jiang, H., Pan, Y., Gu, K., Cang, S. and Han, L. (2021) LBA53 Sintilimab plus Chemotherapy (Chemo) versus Chemo as First-Line Treatment for Advanced Gastric or Gastroesophage-al Junction (G/GEJ) Adenocarcinoma (ORIENT- 16): First Results of a Randomized, Double-Blind, Phase III Study. Annals of Oncology, 32, S1331. [Google Scholar] [CrossRef
[38] Grierson, P., Lim, K.-H. and Amin, M. (2017) Immunotherapy in Gastrointestinal Cancers. Journal of Gastrointestinal Oncology, 8, 474-484. [Google Scholar] [CrossRef] [PubMed]
[39] Karlsson, M., Marits, P., Dahl, K., Dagöö, T., Enerbäck, S. and Thörn, M. (2010) Pilot Study of Sentinel-Node-Based Adoptive Immunotherapy in Advanced Colorectal Cancer. Annals of Surgical Oncology, 17, 1747-1757. [Google Scholar] [CrossRef] [PubMed]