Status and progress of PD-1/PD-L1 blockades for treatment of advanced gastric cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Yicheng ,  LI Yang , LIU Guangyi

Department of Gastrointestinal and Anorectal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China;

Corresponding author：

LI Yang, Email: liyang_68813@126.com

Keywords：

advanced gastric cancer; programmed cell death-1/programmed cell death ligand-1 blockade; biomarker; drug resistance

DOI：

10.7507/1007-9424.202211034

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the clinical value of immunotherapeutic drugs represented by programmed cell death-1 (PD-1) / programmed cell death ligand-1 (PD-L1) blockades for treatment of advanced gastric cancer. Method The latest literatures about the clinical studies of PD-1/PD-L1 blockades for the treatment of advanced gastric cancer were retrieved and reviewed. Results The corresponding clinical trials relevant to PD-1/PD-L1 blockades had been conducted in the treatment, biomarkers, and resistance to drugs for advanced gastric cancer. The PD-1/PD-L1 blockades single drug or its in combination with chemical drugs or (and) targeted drugs for the treatment of advanced gastric cancer or gastroesophageal junction cancer had shown a good efficacy in some patients. The patients who benefited from PD-1/PD-L1 blockades might be a population with specific molecular characteristics, but the resistance to drugs during the therapy process affected its therapeutic effect. Conclusion From the progress of this review, PD-1/PD-L1 blockades bring benefits to some patients with advanced gastric cancer, but more biomarkers which can predict the therapeutic effect need to be found to optimize the drug regimen, and the resistance to drugs mechanism needs to be further studied.

Citation： WANG Yicheng, LI Yang, LIU Guangyi. Status and progress of PD-1/PD-L1 blockades for treatment of advanced gastric cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(5): 626-634. doi: 10.7507/1007-9424.202211034 Copy

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2. Smyth EC, Nilsson M, Grabsch HI, et al. Gastric cancer. Lancet, 2020, 396(10251): 635-648.
3. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med, 2010, 363(8): 711-723.
4. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med, 2012, 366(26): 2455-2465.
5. Dong P, Xiong Y, Yue J, et al. Tumor-intrinsic PD-L1 signaling in cancer initiation, development and treatment: beyond immune evasion. Front Oncol, 2018, 8: 386. doi: 10.3389/fonc.2018.00386.
6. McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med, 2013, 2(5): 662-673.
7. Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol, 2018, 18(3): 153-167.
8. 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. Lancet Oncol, 2016, 17(6): 717-726.
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11. 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. Lancet, 2018, 392(10142): 123-133.
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13. Wainberg ZA, Shitara K, Van Cutsem E, et al. Pembrolizumab with or without chemotherapy versus chemotherapy alone for patients with PD-L1-positive advanced gastric or gastroesophageal junction adenocarcinoma: update from the phase 3 KEYNOTE-062 trial. J Clin Oncol 2022, 40 (4_suppl ): 243. doi.org/10.1200/JCO.2022.40.4_suppl.243.
14. Chung HC, Kang YK, Chen Z, et al. Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): a randomized, open-label, phase 3 trial in Asian patients. Cancer, 2022, 128(5): 995-1003.
15. 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. Lancet, 2017, 390(10111): 2461-2471.
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17. Moehler M, Dvorkin M, Boku N, et al. Phase Ⅲ trial of avelumab maintenance after first-line induction chemotherapy versus continuation of chemotherapy in patients with gastric cancers: results from JAVELIN Gastric 100. J Clin Oncol, 2021, 39(9): 966-977.
18. Zitvogel L, Galluzzi L, Smyth MJ, et al. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity, 2013, 39(1): 74-88.
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20. Bang YJ, Kang YK, Catenacci DV, et al. 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 nonrandomized KEYNOTE-059 study. Gastric Cancer, 2019, 22(4): 828-837.
21. 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. JAMA Oncol, 2020, 6(10): 1571-1580.
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29. Namboodiri AM, Pandey JP. Differential inhibition of trastuzumab- and cetuximab-induced cytotoxicity of cancer cells by immunoglobulin G1 expressing different GM allotypes. Clin Exp Immunol, 2011, 166(3): 361-365.
30. Lordick F, Mariette C, Haustermans K, et al. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2016, 27(suppl 5): v50-v57. doi: 10.1093/annonc/mdw329.
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34. Catenacci DVT, Kang YK, Park H, et al. Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22-05): a single-arm, phase 1b-2 trial. Lancet Oncol, 2020, 21(8): 1066-1076.
35. Catenacci DVT, Rosales MK, Chung HC, et al. Margetuximab (M) combined with anti-PD-1 (retifanlimab) or anti-PD-1/LAG-3 (tebotelimab)+/- chemotherapy (CTX) in first-line therapy of advanced/metastatic HER2+ gastroesophageal junction (GEJ) or gastric cancer (GC). J Clin Oncol, 2021, 39(3_suppl): TPS264. doi:10.1200/JCO.2021.39.3_suppl.TPS264.
36. Catenacci DVT, Kang YK, Yoon HH, et al. Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A. ESMO Open, 2022, 7(5): 100563. doi: 10.1016/j.esmoop.2022.100563.
37. Roland CL, Lynn KD, Toombs JE, et al. Cytokine levels correlate with immune cell infiltration after anti-VEGF therapy in preclinical mouse models of breast cancer. PLoS One, 2009, 4(11): e7669. doi: 10.1371/journal.pone.0007669.
38. Doleschel D, Hoff S, Koletnik S, et al. Regorafenib enhances anti-PD1 immunotherapy efficacy in murine colorectal cancers and their combination prevents tumor regrowth. J Exp Clin Cancer Res, 2021, 40(1): 288. doi: 10.1186/s13046-021-02043-0.
39. Nakajima TE, Kadowaki S, Minashi K, et al. Multicenter phase Ⅰ/Ⅱ study of nivolumab combined with paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer. Clin Cancer Res, 2021, 27(4): 1029-1036.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Status and progress of PD-1/PD-L1 blockades for treatment of advanced gastric cancer

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