Progress on the study of programmed cell death receptor 1 inhibitors for advanced gastric cancer

doi:10.3877/cma.j.issn.1674-0793.2022.05.015

Abstract

Abstract:

Gastric cancer is one of the most common malignant tumors in the upper digestive tract. For early gastric cancer, the effect of surgery combined with chemotherapy is significant, but for advanced gastric cancer (AGC), the effect is not ideal. The emergence of programmed cell death receptor 1 (PD-1) inhibitors provides a new concept for tumor therapy. Studies have shown that PD-1 inhibitors alone have limited efficacy on AGC, and combined therapy with other therapies will have greater clinical benefits. Based on the current research on the application of PD-1 inhibitors in gastric cancer, this paper reviews the research progress of PD-1 inhibitors combined with other therapies in the treatment of AGC.

Key words: PD-1 inhibitors, Immunity therapy, Advanced gastric cancer, Combination therapy

Lining Shang, Chengzhou Du, Gang Guo, Dehe Chen, Jie Wang, Peng Chen, Hongtao Li. Progress on the study of programmed cell death receptor 1 inhibitors for advanced gastric cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2022, 16(05): 376-381.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhptwkxwx.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0793.2022.05.015

https://zhptwkxwx.cma-cmc.com.cn/EN/Y2022/V16/I05/376

Figures/Tables 1

References 36

[1]	Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2]	Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial[J]. Lancet, 2021, 398(10294): 27-40.
[3]	Song Z, Wu Y, Yang J, et al. Progress in the treatment of advanced gastric cancer[J]. Tumor Biol, 2017, 39(7): 1010428317714626.
[4]	Yazici O, Sendur MA, Ozdemir N, et al. Targeted therapies in gastric cancer and future perspectives[J]. World J Gastroenterol, 2016, 22(2): 471-489.
[5]	Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade[J]. Science, 2018, 359(6382): 1350-1355.
[6]	Sun L, Zhang L, Yu J, et al. 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[J]. Sci Rep, 2020, 10(1): 2083.
[7]	Muro K, Chung HC, Shankaran V, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): A multicentre, open-label, phase 1b trial[J]. Lancet Oncol, 2016, 17(6): 717-726.
[8]	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.
[9]	Bass AJ, Thorsson V, Shmulevich I, et al. Comprehensive molecular characterization of gastric adenocarcinoma[J]. Nature, 2014, 513: 202-209.
[10]	Derks S, de Klerk LK, Xu X, et al. Characterizing diversity in the tumor-immune microenvironment of distinct subclasses of gastroesophageal adenocarcinomas[J]. Ann Oncol, 2020, 31(8): 1011-1020.
[11]	Xie J, Fu L, Jin L. Immunotherapy of gastric cancer: past, future perspective and challenges[J]. Pathol Res Pract, 2021, 218: 153322.
[12]	祁玲，黄镜. PD-1/PD-L1抑制剂在晚期胃癌治疗中的临床研究进展[J]. 中国生化药物杂志, 2016, 36(7): 4-7.
[13]	National Cancer Institute. Immune checkpoint inhibitors[EB/OL]. URL
[14]	Shitara K, Van Cutsem E, Bang YJ, et al. 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[J]. JAMA Oncol, 2020, 6(10): 1571-1580.
[15]	Shitara K, özgüroğlu M, Bang YJ, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): A randomised, open-label, controlled, phase 3 trial[J]. Lancet, 2018, 392(10142): 123-133.
[16]	Chen T, Satoh T, Ryu MH, et al. A phase Ⅲ study of Nivolumab (NIVO) in previously treated advanced gastric or gastricesophageal junction (G/GEJ) cancer (ATTRACTION-02): 2-year update data[J]. Gastr Cancer, 2019, 23(3): 510-519.
[17]	Vacchelli E, Aranda F, Eggermont A, et al. Trial watch: chemotherapy with immunogenic cell death inducers[J]. Oncoimmunology, 2014, 3(1): e27878.
[18]	Fuchs CS, Doi T, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial[J]. JAMA Oncol, 2018, 4(5): e180013.
[19]	Xu J, Jiang H, Pan Y, et al. LBA53 Sintilimab plus chemotherapy (chemo) versus chemo as first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ORIENT-16): first results of a randomized, double-blind, phase Ⅲ study[J]. Ann Oncol, 2021, 32: S1331.
[20]	Corraliza-Gorjón I, Somovilla-Crespo B, Santamaria S, et al. New strategies using antibody combinations to increase cancer treatment effectiveness[J]. Front Immunol, 2017, 8: 1804.
[21]	Janjigian YY, Kawazoe A, Yañez P, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer[J]. Nature, 2021, 600(7890): 727-730.
[22]	Catenacci DV, Rosales M, Chung HC, et al. MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma[J]. Future Oncol, 2021, 17(10): 1155-1164.
[23]	Rotte A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer[J]. J Exp Clin Cancer Res, 2019, 38(1): 255.
[24]	Janjigian YY, Bendell J, Calvo E, et al. CheckMate-032 study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer[J]. J Clin Oncol, 2018, 36(28): 2836-2844.
[25]	Kato Y, Tabata K, Kimura T, et al. Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway[J]. PLoS One, 2019, 14(2): e0212513.
[26]	Fukuoka S, Hara H, Takahashi N, et al. Regorafenib plus nivolumab in patients with advanced gastric or colorectal cancer: An open-label, dose-escalation, and dose-expansion phase Ⅰb trial (REGONIVO, EPOC1603)[J]. J Clin Oncol, 2020, 38(18): 2053-2061.
[27]	Kawazoe A, Fukuoka S, Nakamura Y, et al. Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): An open-label, single-arm, phase 2 trial[J]. Lancet Oncol, 2020, 21(8): 1057-1065.
[28]	Tang C, Wang X, Soh H. et al. Combining radiation and immunotherapy: A new systemic therapy for solid tumors?[J]. Cancer Immunol Res, 2014, 2(9): 831-838.
[29]	Qi C, Gong J, Li J, et al. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results[J]. Clinical Trial Nat Med, 2022, 28(6): 1189-1198.
[30]	Wall JA, Klempner SJ, Arend RC. The anti-DKK1 antibody DKN-01 as an immunomodulatory combination partner for the treatment of cancer[J]. Expert Opin Investig Drugs, 2020, 29(7): 639-644.
[31]	Yanai H, Ban T, Wang Z, et al. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses[J]. Nature, 2009, 462(7269): 99-103.
[32]	Le DT, Uram JN, Wang H. et al. PD-1 blockade in tumors with mismatch-repair deficiency[J]. N Eng J Med, 2015, 372(26): 2509-2520.
[33]	Fuchs CS, Doi T, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 cinical KEYNOTE-059 trial[J]. JAMA Oncol, 2018, 4(5): e180013.
[34]	Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J]. Science, 2018, 359(6371): 91-97.
[35]	Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer[J]. CA Cancer J Clin, 2021, 71(3): 264-279.
[36]	Geoerger B, Kang HJ, Yalon-Oren M, et al. Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial[J]. Lancet Oncol, 2020, 21(1): 121-133.

Please choose a citation manager

Content to export