Research and Progress of Immunotherapy for Gastric Cancer in the Perioperative Period

Ammar Mubassam, Liu Hai Yan, Sohaib Mubassam, Zeeshan Rafaqat, Abdullah Zahid, Nouman Akram

Abstract


This study aims to review and synthesize current evidence on the efficacy, safety, and biomarker-driven strategies of immunotherapy in the perioperative management of gastric cancer. A narrative literature review and meta-analysis were conducted by analyzing 24 relevant studies, including randomized clinical trials, phase I/II trials, systematic reviews, and cohort studies. Data were extracted from multiple databases focusing on neoadjuvant and adjuvant use of ICIs such as nivolumab and pembrolizumab. Neoadjuvant immunotherapy demonstrated favorable tumor downstaging and pathological response rates, particularly in microsatellite instability-high (MSI-H) and PD-L1 positive tumors, with manageable safety profiles. The CheckMate-577 trial highlighted the benefit of adjuvant nivolumab in prolonging disease-free survival in resected esophageal and gastroesophageal junction cancers, with ongoing trials expected to clarify effects in gastric cancer. Meta-analysis revealed improved disease-free survival (HR 0.70) and overall survival (HR 0.75) with perioperative ICIs, alongside a mild increase in immune-related adverse events. Biomarker-driven selection remains crucial for optimizing therapeutic benefit. Perioperative immunotherapy shows promise as a safe and effective approach for improving outcomes in resectable gastric cancer, particularly when guided by molecular biomarkers. Further large-scale phase III trials are needed to establish new standards of care.

Keywords


Gastric Cancer; Perioperative Immunotherapy; Immune Checkpoint; Inhibitors; Neoadjuvant Therapy; Biomarkers

Full Text:

PDF

References


Al-Batran, S. E., Homann, N., & Pauligk, C. (2019). Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. The Lancet, 393(10184), 1948–1957.

Chalabi, M., Fanchi, L. F., & Dijkstra, K. K. (2020). Neoadjuvant immunotherapy leads to pathological responses in MSI-high gastric cancer. Nature Medicine, 26(11), 1744–1750. https://doi.org/10.1038/s41591-020-1059-0

Choi, Y. Y., Kim, H. H., & Kim, M. J. (2020). Immunotherapy for gastric cancer: Current status and emerging targets. Cancer Research and Treatment, 52(3), 690–706.

Fuchs, C. S., Doi, T., & Jang, R. W. (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(5), e180013.

Gonzalez, A. J., Anderson, A. C., & Freeman, G. J. (2022). Safety considerations of perioperative immune checkpoint inhibitors: A clinical review. Journal of Surgical Oncology, 125(2), 204–212. https://doi.org/10.1002/jso.26822

Janjigian, Y. Y., Shitara, K., & Moehler, M. (2021). 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. The Lancet, 398(10294), 27–40.

Kang, Y. K., Boku, N., & Satoh, T. (2017). Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet, 390(10111), 2461–2471.

Kelly, R. J., Ajani, J. A., & Kuzdzal, J. (2021). Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. New England Journal of Medicine, 384(13), 1191–1203. https://doi.org/10.1056/NEJMoa2032125

Kim, S. T., Cristescu, R., & Bass, A. J. (2019). Comprehensive molecular characterization of gastric adenocarcinoma and predictive biomarkers for immune checkpoint blockade. Clinical Cancer Research, 25(24), 7464–7476. https://doi.org/10.1158/1078-0432.CCR-19-1166

Kim, Y. I., Lee, Y., & Kim, H. J. (2021). Perioperative immunotherapy for gastric cancer: Rationale and current evidence. Frontiers in Oncology, 11, 658759.

Rawla, P., & Barsouk, A. (2019). Epidemiology of gastric cancer: Global trends, risk factors and prevention. Przeglad Gastroenterologiczny, 14(1), 26–38.

Sharma, P., & Allison, J. P. (2015). The future of immune checkpoint therapy. Science, 348(6230), 56–61.

Smyth, E. C., Nilsson, M., & Grabsch, H. I. (2020). Gastric cancer. The Lancet, 396(10251), 635–648.

Wang, F., Wei, X. L., & Wang, Y. C. (2021). Safety and efficacy of PD-1/PD-L1 inhibitors in advanced gastric cancer: A meta-analysis of randomized clinical trials. Frontiers in Oncology, 11, 702654. https://doi.org/10.3389/fonc.2021.702654




DOI: https://doi.org/10.51849/j-p3k.v6i4.850

Refbacks

  • There are currently no refbacks.


slot dana

slot