Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology

Authors:
Jaffer A. Ajani The University of Texas MD Anderson Cancer Center

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Thomas A. D’Amico Duke Cancer Institute

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David J. Bentrem Robert H. Lurie Comprehensive Cancer Center of Northwestern University

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Carlos U. Corvera UCSF Helen Diller Family Comprehensive Cancer Center

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Prajnan Das The University of Texas MD Anderson Cancer Center

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Peter C. Enzinger Dana-Farber/Brigham and Women’s Cancer Center

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Thomas Enzler University of Michigan Rogel Cancer Center

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Hans Gerdes Memorial Sloan Kettering Cancer Center

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Michael K. Gibson Vanderbilt-Ingram Cancer Center

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Patrick Grierson Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

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Garima Gupta O’Neal Comprehensive Cancer Center at UAB

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Wayne L. Hofstetter The University of Texas MD Anderson Cancer Center

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David H. Ilson Memorial Sloan Kettering Cancer Center

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Shadia Jalal Indiana University Melvin and Bren Simon Comprehensive Cancer Center

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Sunnie Kim University of Colorado Cancer Center

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Lawrence R. Kleinberg Johns Hopkins Kimmel Cancer Center

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Samuel Klempner Mass General Cancer Center

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Jill Lacy Yale Cancer Center/Smilow Cancer Hospital

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Byrne Lee Stanford Cancer Institute

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Frank Licciardi Patient Advocate

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Shane Lloyd Huntsman Cancer Institute at the University of Utah

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Quan P. Ly Fred & Pamela Buffett Cancer Center

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Karen Matsukuma UC Davis Comprehensive Cancer Center

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Michael McNamara Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute

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Ryan P. Merkow The UChicago Medicine Comprehensive Cancer Center

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Aaron M. Miller UC San Diego Moores Cancer Center

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Sarbajit Mukherjee Roswell Park Comprehensive Cancer Center

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Mary F. Mulcahy Robert H. Lurie Comprehensive Cancer Center of Northwestern University

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Kyle A. Perry The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute

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Jose M. Pimiento Moffitt Cancer Center

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Deepti M. Reddi Fred Hutchinson Cancer Center

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Scott Reznik UT Southwestern Simmons Comprehensive Cancer Center

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Robert E. Roses Abramson Cancer Center at the University of Pennsylvania

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Vivian E. Strong Memorial Sloan Kettering Cancer Center

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Stacey Su Fox Chase Cancer Center

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Nataliya Uboha University of Wisconsin Carbone Cancer Center

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Zev A. Wainberg UCLA Jonsson Comprehensive Cancer Center

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Christopher G. Willett Duke Cancer Institute

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Yanghee Woo City of Hope National Medical Center

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Harry H. Yoon Mayo Clinic Comprehensive Cancer Center

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Nicole R. McMillian National Comprehensive Cancer Network

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MaryElizabeth Stein National Comprehensive Cancer Network

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Volume/Issue:
Volume 23: Issue 5
Online Publication Date:
May 2025
DOI:
https://doi.org/10.6004/jnccn.2025.0022
Restricted access

Gastric cancer is the fifth leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improve survival, and enhance the quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing has had a significant impact on clinical practice and patient care. Targeted therapies have demonstrated encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. This selection from the NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer highlights recommendations for biomarker testing and discusses updates for the treatment of advanced disease, including peritoneal carcinoma as only disease and unresectable locally advanced, recurrent, or metastatic disease.

Discussion Writing Committee Members:

Jaffer A. Ajani, Thomas A. D’Amico, Nataliya Uboha, Nicole R. McMillian, and MaryElizabeth Stein

To view disclosures of external relationships for the NCCN Guidelines panel, go to https://www.nccn.org/guidelines/guidelines-panels-and-disclosure/disclosure-panels

The full NCCN Guidelines for Gastric Cancer are not printed in this issue of JNCCN. The complete and most recent version of these guidelines is available free of charge at NCCN.org.

NCCN CATEGORIES OF EVIDENCE AND CONSENSUS

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise indicated.

NCCN CATEGORIES OF PREFERENCE

Preferred intervention: Interventions that are based on superior efficacy, safety, and evidence; and, when appropriate, affordability.

Other recommended intervention: Other interventions that may be somewhat less efficacious, more toxic, or based on less mature data; or significantly less affordable for similar outcomes.

Useful in certain circumstances: Other interventions that may be used for selected patient populations (defined with recommendation).

All recommendations are considered appropriate.

NCCN recognizes the importance of clinical trials and encourages participation when applicable and available.

Trials should be designed to maximize inclusiveness and broad representative enrollment.

PLEASE NOTE

The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

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Print ISSN:
1540-1405
Online ISSN:
1540-1413
Publisher:
National Comprehensive Cancer Network
Cover Journal of the National Comprehensive Cancer Network
  • 1.

    Sitarz R, Skierucha M, Mielko J, et al. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res 2018;10:239–248.

  • 2.

    Thrift AP, Wenker TN, El-Serag HB. Global burden of gastric cancer: epidemiological trends, risk factors, screening and prevention. Nat Rev Clin Oncol 2023;20:338–349.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Ma J, Shen H, Kapesa L, Zeng S. Lauren classification and individualized chemotherapy in gastric cancer. Oncol Lett 2016;11:2959–2964.

  • 4.

    National Cancer Institute. Cancer stat facts: stomach cancer. Accessed May 6, 2024. Available at https://seer.cancer.gov/statfacts/html/stomach.html

  • 5.

    Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends--an update. Cancer Epidemiol Biomarkers Prev 2016;25:16–27.

  • 6.

    Etemadi A, Safiri S, Sepanlou SG, et al. The global, regional, and national burden of stomach cancer in 195 countries, 1990–2017: a systematic analysis for the Global Burden of Disease study 2017. Lancet Gastroenterol Hepatol 2020;5:42–54.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74:229–263.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    World Health Organization. GLOBOCAN 2022: stomach cancer fact sheet. Accessed May 8, 2024. Available at https://gco.iarc.who.int/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Zhao JK, Wu M, Kim CH, et al. Jiangsu Four Cancers Study: a large case-control study of lung, liver, stomach, and esophageal cancers in Jiangsu Province, China. Eur J Cancer Prev 2017;26:357–364.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Siegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025. CA Cancer J Clin 2025;75:10–45.

  • 11.

    Bergquist JR, Leiting JL, Habermann EB, et al. Early-onset gastric cancer is a distinct disease with worrisome trends and oncogenic features. Surgery 2019;166:547–555.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Arnold M, Park JY, Camargo MC, et al. Is gastric cancer becoming a rare disease? A global assessment of predicted incidence trends to 2035. Gut 2020;69:823–829.

  • 13.

    Li Y, Hahn AI, Laszkowska M, et al. Clinicopathological characteristics and risk factors of young-onset gastric carcinoma: a systematic review and meta-analysis. Clin Transl Gastroenterol 2024;15:e1.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Karimi P, Islami F, Anandasabapathy S, et al. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev 2014;23:700–713.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Yusefi AR, Bagheri Lankarani K, Bastani P, et al. Risk factors for gastric cancer: a systematic review. Asian Pac J Cancer Prev 2018;19:591–603.

  • 16.

    Hu B, El Hajj N, Sittler S, et al. Gastric cancer: classification, histology and application of molecular pathology. J Gastrointest Oncol 2012;3:251–261.

  • 17.

    Tramacere I, Negri E, Pelucchi C, et al. A meta-analysis on alcohol drinking and gastric cancer risk. Ann Oncol 2012;23:28–36.

  • 18.

    He Z, Zhao TT, Xu HM, et al. Association between alcohol consumption and the risk of gastric cancer: a meta-analysis of prospective cohort studies. Oncotarget 2017;8:84459–84472.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Wang PL, Xiao FT, Gong BC, Liu FN. Alcohol drinking and gastric cancer risk: a meta-analysis of observational studies. Oncotarget 2017;8:99013–99023.

  • 20.

    Deng W, Jin L, Zhuo H, et al. Alcohol consumption and risk of stomach cancer: a meta-analysis. Chem Biol Interact 2021;336:109365.

  • 21.

    Falk J, Carstens H, Lundell L, Albertsson M. Incidence of carcinoma of the oesophagus and gastric cardia. Changes over time and geographical differences. Acta Oncol 2007;46:1070–1074.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Powell J, McConkey CC, Gillison EW, Spychal RT. Continuing rising trend in oesophageal adenocarcinoma. Int J Cancer 2002;102:422–427.

  • 23.

    Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol 2006;12:354–362.

  • 24.

    Brar SS, Mahar AL, Helyer LK, et al. Processes of care in the multidisciplinary treatment of gastric cancer: results of a RAND/UCLA expert panel. JAMA Surg 2014;149:18–25.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Siewert JR. Carcinoma of the cardia: carcinoma of the gastroesophageal junction classification, pathology, and extent of resection. Dis Esophagus 1996;9:173–182.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Siewert JR, Feith M, Werner M, Stein HJ. Adenocarcinoma of the esophagogastric junction: results of surgical therapy based on anatomical/ topographic classification in 1,002 consecutive patients. Ann Surg 2000;232:353–361.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014;513:202–209.

  • 28.

    Nemtsova MV, Kuznetsova EB, Bure IV. Chromosomal instability in gastric cancer: role in tumor development, progression, and therapy. Int J Mol Sci 2023;24:16961.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Supek F, Lehner B. Differential DNA mismatch repair underlies mutation rate variation across the human genome. Nature 2015;521:81–84.

  • 30.

    Puliga E, Corso S, Pietrantonio F, Giordano S. Microsatellite instability in gastric cancer: between lights and shadows. Cancer Treat Rev 2021;95:102175.

  • 31.

    Wang L, Zhang Q, Ni S, et al. Programmed death-ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER2-negative status. Cancer Med 2018;7:2612–2620.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Morihiro T, Kuroda S, Kanaya N, et al. PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer. Sci Rep 2019;9:4633.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Hechtman JF, Polydorides AD. HER2/neu gene amplification and protein overexpression in gastric and gastroesophageal junction adenocarcinoma: a review of histopathology, diagnostic testing, and clinical implications. Arch Pathol Lab Med 2012;136:691–697.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Chua TC, Merrett ND. Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes--a systematic review. Int J Cancer 2012;130:2845–2856.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Gómez-Martin C, Garralda E, Echarri MJ, et al. HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer. J Clin Pathol 2012;65:751–757.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Jørgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer-a systematic analysis of data from the literature. J Cancer 2012;3:137–144.

  • 37.

    Kato S, Okamura R, Baumgartner JM, et al. Analysis of circulating tumor DNA and clinical correlates in patients with esophageal, gastroesophageal junction, and gastric adenocarcinoma. Clin Cancer Res 2018;24:6248–6256.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Cho JH, Lim JY, Cho JY. Survival analysis based on human epidermal growth factor 2 status in stage II–III gastric cancer. World J Gastroenterol 2017;23:7407–7414.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Lei YY, Huang JY, Zhao QR, et al. The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature. World J Surg Oncol 2017;15:68.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Grabsch H, Sivakumar S, Gray S, et al. HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value-conclusions from 924 cases of two independent series. Cell Oncol 2010;32:57–65.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Janjigian YY, Werner D, Pauligk C, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA international collaborative analysis. Ann Oncol 2012;23:2656–2662.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Kunz PL, Mojtahed A, Fisher GA, et al. HER2 expression in gastric and gastroesophageal junction adenocarcinoma in a US population: clinicopathologic analysis with proposed approach to HER2 assessment. Appl Immunohistochem Mol Morphol 2012;20:13–24.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Scheck MK, Hofheinz RD, Lorenzen S. HER2-positive gastric cancer and antibody treatment: state of the art and future developments. Cancers (Basel) 2024;16:1336.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Tanner M, Hollmen M, Junttila TT, et al. Amplification of HER-2 in gastric carcinoma: association with topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 2005;16:273–278.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Yan B, Yau EX, Bte Omar SS, et al. A study of HER2 gene amplification and protein expression in gastric cancer. J Clin Pathol 2010;63:839–842.

  • 46.

    Kim WH, Gomez-Izquierdo L, Vilardell F, et al. HER2 status in gastric and gastroesophageal junction cancer: results of the large, multinational HER-EAGLE study. Appl Immunohistochem Mol Morphol 2018;26:239–245.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer 2015;18:476–484.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376:687–697.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    Bartley AN, Washington MK, Colasacco C, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol 2017;35:446–464.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50.

    Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008;52:797–805.

  • 51.

    Ruschoff J, Dietel M, Baretton G, et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch 2010;457:299–307.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52.

    Wu H, Ma W, Jiang C, et al. Heterogeneity and adjuvant therapeutic approaches in MSI-H/dMMR resectable gastric cancer: emerging trends in immunotherapy. Ann Surg Oncol 2023;30:8572–8587.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    Polom K, Marano L, Marrelli D, et al. Meta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer. Br J Surg 2018;105:159–167.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54.

    Bermúdez A, Arranz-Salas I, Mercado S, et al. Her2-positive and microsatellite instability status in gastric cancer-clinicopathological implications. Diagnostics (Basel) 2021;11:944.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55.

    Mathiak M, Warneke VS, Behrens HM, et al. Clinicopathologic characteristics of microsatellite instable gastric carcinomas revisited: Urgent need for standardization. Appl Immunohistochem Mol Morphol 2017;25:12–24.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56.

    Bonneville R, Krook MA, Kautto EA, et al. Landscape of microsatellite instability across 39 cancer types. JCO Precis Oncol. Published online October 3, 2017. doi:10.1200/PO.17.00073

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57.

    Pietrantonio F, Miceli R, Raimondi A, et al. Individual patient data meta-analysis of the value of microsatellite instability as a biomarker in gastric cancer. J Clin Oncol 2019;37:3392–3400.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58.

    Chao J, Fuchs CS, Shitara K, et al. Assessment of pembrolizumab therapy for the treatment of microsatellite instability-high gastric or gastroesophageal junction cancer among patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 clinical trials. JAMA Oncol 2021;7:895–902.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 59.

    Zhuo ZG, Deng HY, Song TN, et al. Predictors for the clinical benefit of anti-PD-1/PD-L1 therapy in advanced gastroesophageal cancer: a meta-analysis of clinical trials. Ann Palliat Med 2020;9:2524–2537.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 60.

    Ratti M, Lampis A, Hahne JC, et al. Microsatellite instability in gastric cancer: molecular bases, clinical perspectives, and new treatment approaches. Cell Mol Life Sci 2018;75:4151–4162.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 61.

    Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357:409–413.

  • 62.

    Bartley AN, Fitzgibbons PL, Broaddus RR, Shi C. Template for reporting results of DNA mismatch repair testing in patients being considered for checkpoint inhibitor immunotherapy. Accessed March 31, 2025. Available at https://documents.cap.org/protocols/cp-dnamismatchrepair-18biomarker-1000.pdf

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 63.

    Gou Q, Dong C, Xu H, et al. PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis 2020;11:955.

  • 64.

    Cha JH, Chan LC, Li CW, et al. Mechanisms controlling PD-L1 expression in cancer. Mol Cell 2019;76:359–370.

  • 65.

    Lin X, Kang K, Chen P, et al. Regulatory mechanisms of PD-1/PD-L1 in cancers. Mol Cancer 2024;23:108.

  • 66.

    Liu X, Choi MG, Kim K, et al. High PD-L1 expression in gastric cancer (GC) patients and correlation with molecular features. Pathol Res Pract 2020;216:152881.

  • 67.

    Boger C, Behrens HM, Mathiak M, et al. PD-L1 is an independent prognostic predictor in gastric cancer of Western patients. Oncotarget 2016;7:24269–24283.

  • 68.

    Chen XJ, Wei CZ, Lin J, et al. Prognostic significance of PD-L1 expression in gastric cancer patients with peritoneal metastasis. Biomedicines 2023;11:2003.

  • 69.

    Gu L, Chen M, Guo D, et al. PD-L1 and gastric cancer prognosis: a systematic review and meta-analysis. PLoS One 2017;12:e0182692.

  • 70.

    Kawazoe A, Kuwata T, Kuboki Y, et al. Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein-Barr virus status in a large cohort of gastric cancer patients. Gastric Cancer 2017;20:407–415.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 71.

    Chang H, Jung WY, Kang Y, et al. Programmed death-ligand 1 expression in gastric adenocarcinoma is a poor prognostic factor in a high CD8+ tumor infiltrating lymphocytes group. Oncotarget 2016;7:80426–80434.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 72.

    Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet 2023;401:1655–1668.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 73.

    Angerilli V, Ghelardi F, Nappo F, et al. Claudin-18.2 testing and its impact in the therapeutic management of patients with gastric and gastroesophageal adenocarcinomas: a literature review with expert opinion. Pathol Res Pract 2024;254:155145.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 74.

    Pellino A, Brignola S, Riello E, et al. Association of CLDN18 protein expression with clinicopathological features and prognosis in advanced gastric and gastroesophageal junction adenocarcinomas. J Pers Med 2021;11:1095.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 75.

    Coati I, Lotz G, Fanelli GN, et al. Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases. Br J Cancer 2019;121:257–263.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 76.

    Kubota Y, Kawazoe A, Mishima S, et al. Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer. ESMO Open 2023;8:100762.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 77.

    Shitara K, Xu RH, Ajani JA, et al. Global prevalence of claudin 18 isoform 2 in tumors of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Gastric Cancer 2024;27:1058–1068.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 78.

    Cao W, Xing H, Li Y, et al. Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy. Biomark Res 2022;10:38.

  • 79.

    Rohde C, Yamaguchi R, Mukhina S, et al. Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma. Jpn J Clin Oncol 2019;49:870–876.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 80.

    Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res 2008;14:7624–7634.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 81.

    Inamoto R, Takahashi N, Yamada Y. Claudin18.2 in advanced gastric cancer. Cancers (Basel) 2023;15:5742.

  • 82.

    Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med 2023;29:2133–2141.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 83.

    Willis J, Lefterova MI, Artyomenko A, et al. Validation of microsatellite instability detection using a comprehensive plasma-based genotyping panel. Clin Cancer Res 2019;25:7035–7045.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 84.

    Brandl A, van Sandick JW. Treatment of gastric cancer peritoneal metastases: role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Br J Surg 2024;111:znae149.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 85.

    Manzanedo I, Pereira F, Pérez-Viejo E, Serrano A. Gastric cancer with peritoneal metastases: Current status and prospects for treatment. Cancers (Basel) 2023;15:1777.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 86.

    Bonnot PE, Piessen G, Kepenekian V, et al. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastases (CYTO-CHIP study): a propensity score analysis. J Clin Oncol 2019;37:2028–2040.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 87.

    Badgwell B, Ikoma N, Murphy MB, et al. A phase II trial of cytoreduction, gastrectomy, and hyperthermic intraperitoneal perfusion with chemotherapy for patients with gastric cancer and carcinomatosis or positive cytology. Ann Surg Oncol 2021;28:258–264.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 88.

    Yang XJ, Huang CQ, Suo T, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol 2011;18:1575–1581.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 89.

    Rau B, Lang H, Koenigsrainer A, et al. Effect of hyperthermic intraperitoneal chemotherapy on cytoreductive surgery in gastric cancer with synchronous peritoneal metastases: the phase III Gastripec-I trial. J Clin Oncol 2024;42:146–156.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 90.

    Sarvestani AL, Gregory SN, Akmal SR, et al. Gastrectomy + cytoreductive surgery + hipec for gastric cancer with peritoneal dissemination (PERISCOPE II). Ann Surg Oncol 2024;31:28–30.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 91.

    Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM, ed. Evaluation of Chemotherapeutic Agents. New York Columbia University Press; 1949:199–205.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 92.

    Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–656.

  • 93.

    Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity, and guidelines. J Clin Oncol 1984;2:187–193.

  • 94.

    Glimelius B, Ekstrom K, Hoffman K, et al. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 1997;8:163–168.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 95.

    Thuss-Patience PC, Kretzschmar A, Bichev D, et al. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer–a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 2011;47:2306–2314.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 96.

    Kang JH, Lee SI, Lim DH, et al. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 2012;30:1513–1518.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 97.

    Ford ER, Marshall A, Bridgewater JA, et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol 2014;15:78–86.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 98.

    Conroy T, Galais MP, Raoul JL, et al. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol 2014;15:305–314.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 99.

    Khushalani NI, Leichman CG, Proulx G, et al. Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: report of a clinical trial for patients with esophageal cancer. J Clin Oncol 2002;20:2844–2850.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 100.

    Bedenne L, Michel P, Bouche O, et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 2007;25:1160–1168.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 101.

    Ajani JA, Winter K, Okawara GS, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 2006;24:3953–3958.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 102.

    Al-Batran SE, Pauligk C, Homann N, et al. The feasibility of triple-drug chemotherapy combination in older adult patients with oesophagogastric cancer: a randomised trial of the Arbeitsgemeinschaft Internistische Onkologie (FLOT65+). Eur J Cancer 2013;49:835–842.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 103.

    Al-Batran S-E, Hartmann JT, Probst S, et al. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol 2008;26:1435–1442.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 104.

    Enzinger PC, Burtness BA, Niedzwiecki D, et al. CALGB 80403 (Alliance)/E1206: a randomized phase II study of three chemotherapy regimens plus cetuximab in metastatic esophageal and gastroesophageal junction cancers. J Clin Oncol 2016;34:2736–2742.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 105.

    Kim GM, Jeung HC, Rha SY, et al. A randomized phase II trial of S-1- oxaliplatin versus capecitabine-oxaliplatin in advanced gastric cancer. Eur J Cancer 2012;48:518–526.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 106.

    Lorenzen S, Schuster T, Porschen R, et al. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol 2009;20:1667–1673.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 107.

    Bouche O, Raoul JL, Bonnetain F, et al. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study-FFCD 9803. J Clin Oncol 2004;22:4319–4328.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 108.

    Kang YK, Kang WK, Shin DB, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol 2009;20:666–673.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 109.

    Louvet C, Andre T, Tigaud JM, et al. Phase II study of oxaliplatin, fluorouracil, and folinic acid in locally advanced or metastatic gastric cancer patients. J Clin Oncol 2002;20:4543–4548.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 110.

    Al-Batran S-E, Atmaca A, Hegewisch-Becker S, et al. Phase II trial of biweekly infusional fluorouracil, folinic acid, and oxaliplatin in patients with advanced gastric cancer. J Clin Oncol 2004;22:658–663.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 111.

    Park YH, Lee JL, Ryoo BY, et al. Capecitabine in combination with oxaliplatin (XELOX) as a first-line therapy for advanced gastric cancer. Cancer Chemother Pharmacol 2008;61:623–629.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 112.

    Luo HY, Xu RH, Wang F, et al. Phase II trial of XELOX as first-line treatment for patients with advanced gastric cancer. Chemotherapy 2010;56:94–100.

  • 113.

    Okines AFC, Norman AR, McCloud P, et al. Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol 2009;20:1529–1534.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 114.

    Wang G, Yang B, Fu Z, et al. Efficacy and safety of oxaliplatin-based regimen versus cisplatin-based regimen in the treatment of gastric cancer: a meta-analysis of randomized controlled trials. Int J Clin Oncol 2019;24:614–623.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 115.

    Hall PS, Swinson D, Cairns DA, et al. Efficacy of reduced-intensity chemotherapy with oxaliplatin and capecitabine on quality of life and cancer control among older and frail patients with advanced gastroesophageal cancer: the GO2 phase 3 randomized clinical trial. JAMA Oncol 2021;7:869–877.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 116.

    Enzinger PC, Kulke MH, Clark JW, et al. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci 2005;50:2218–2223.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 117.

    Ajani JA, Baker J, Pisters PWT, et al. CPT-11 plus cisplatin in patients with advanced, untreated gastric or gastroesophageal junction carcinoma: results of a phase II study. Cancer 2002;94:641–646.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 118.

    Moehler M, Haas U, Siebler J, et al. Weekly treatment with irinotecan, folinic acid and infusional 5-fluorouracil (ILF) in patients with advanced gastric cancer. Anticancer Drugs 2003;14:645–650.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 119.

    Pozzo C, Barone C, Szanto J, et al. Irinotecan in combination with 5- fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol 2004;15:1773–1781.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 120.

    Moehler M, Eimermacher A, Siebler J, et al. Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer. Br J Cancer 2005;92:2122–2128.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 121.

    Beretta E, Di Bartolomeo M, Buzzoni R, et al. Irinotecan, fluorouracil and folinic acid (FOLFIRI) as effective treatment combination for patients with advanced gastric cancer in poor clinical condition. Tumori 2006;92:379–383.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 122.

    Dank M, Zaluski J, Barone C, et al. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol 2008;19:1450–1457.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 123.

    Brell JM, Krishnamurthi SS, Javle M, et al. A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma. Cancer Chemother Pharmacol 2009;63:851–857.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 124.

    Enzinger PC, Ryan DP, Clark JW, et al. Weekly docetaxel, cisplatin, and irinotecan (TPC): results of a multicenter phase II trial in patients with metastatic esophagogastric cancer. Ann Oncol 2009;20:475–480.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 125.

    Lustberg MB, Bekaii-Saab T, Young D, et al. Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. J Thorac Oncol 2010;5:713–718.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 126.

    Moehler M, Kanzler S, Geissler M, et al. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol 2010;21:71–77.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 127.

    Guimbaud R, Louvet C, Ries P, et al. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French Intergroup (Federation Francophone de Cancerologie Digestive, Federation Nationale des Centres de Lutte Contre le Cancer, and Groupe Cooperateur Multidisciplinaire en Oncologie) study. J Clin Oncol 2014;32:3520–3526.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 128.

    Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 2006;24:4991–4997.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 129.

    Roth AD, Fazio N, Stupp R, et al. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol 2007;25:3217–3223.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 130.

    Al-Batran SE, Hartmann JT, Hofheinz R, et al. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol 2008;19:1882–1887.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 131.

    Elsaid AA, Elkerm Y. Final results of a randomized phase III trial of docetaxel, carboplatin and 5FU versus epirubicin, cisplatin and 5FU for locally advanced gastric cancer. J Clin Oncol 2005;23(Suppl):Abstract 4014.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 132.

    Inal A, Kaplan MA, Kucukoner M, Isikdogan A. Docetaxel and cisplatin plus fluorouracil compared with modified docetaxel, cisplatin, and 5-fluorouracil as first-line therapy for advanced gastric cancer: a retrospective analysis of single institution. Neoplasma 2012;59:233–236.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 133.

    Di Lauro L, Vici P, Belli F, et al. Docetaxel, oxaliplatin, and capecitabine combination chemotherapy for metastatic gastric cancer. Gastric Cancer 2014;17:718–724.

  • 134.

    Van Cutsem E, Boni C, Tabernero J, et al. Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study. Ann Oncol 2015;26:149–156.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 135.

    Shah MA, Janjigian YY, Stoller R, et al. Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus DCF plus growth factor support in patients with metastatic gastric adenocarcinoma: a study of the US Gastric Cancer Consortium. J Clin Oncol 2015;33:3874–3879.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 136.

    Ilson DH, Forastiere A, Arquette M, et al. A phase II trial of paclitaxel and cisplatin in patients with advanced carcinoma of the esophagus. Cancer J 2000;6:316–323.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 137.

    Petrasch S, Welt A, Reinacher A, et al. Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer. Br J Cancer 1998;78:511–514.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 138.

    Gadgeel SM, Shields AF, Heilbrun LK, et al. Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. Am J Clin Oncol 2003;26:37–41.

  • 139.

    Ajani JA, Fodor MB, Tjulandin SA, et al. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol 2005;23:5660–5667.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 140.

    Kim JY, Do YR, Park KU, et al. A multi-center phase II study of docetaxel plus cisplatin as first-line therapy in patients with metastatic squamous cell esophageal cancer. Cancer Chemother Pharmacol 2010;66:31–36.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 141.

    Blum Murphy MA, Qiao W, Mewada N, et al. A phase I/II study of docetaxel, oxaliplatin, and fluorouracil (D-FOX) chemotherapy in patients with untreated locally unresectable or metastatic adenocarcinoma of the stomach and gastroesophageal junction. Am J Clin Oncol 2018;41:321–325.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 142.

    Ohtsu A, Shimada Y, Shirao K, et al. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 2003;21:54–59.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 143.

    Hong YS, Song SY, Lee SI, et al. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol 2004;15:1344–1347.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 144.

    Albertsson M, Johansson B, Friesland S, et al. Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer. Med Oncol 2007;24:407–412.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 145.

    Ajani JA, Ilson DH, Daugherty K, et al. Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst 1994;86:1086–1091.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 146.

    Ilson DH, Wadleigh RG, Leichman LP, Kelsen DP. Paclitaxel given by a weekly 1-h infusion in advanced esophageal cancer. Ann Oncol 2007;18:898–902.

  • 147.

    Cascinu S, Bodoky G, Muro K, et al. Tumor response and symptom palliation from RAINBOW, a phase III trial of ramucirumab plus paclitaxel in previously treated advanced gastric cancer. Oncologist 2021;26:e414–424.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 148.

    Hironaka S, Ueda S, Yasui H, et al. 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. J Clin Oncol 2013;31:4438–4444.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 149.

    Fuchs CS, Moore MR, Harker G, et al. Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol 2003;21:807–814.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 150.

    Sym SJ, Hong J, Park J, et al. A randomized phase II study of biweekly irinotecan monotherapy or a combination of irinotecan plus 5-fluorouracil/leucovorin (mFOLFIRI) in patients with metastatic gastric adenocarcinoma refractory to or progressive after first-line chemotherapy. Cancer Chemother Pharmacol 2013;71:481–488.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 151.

    Maugeri-Saccà M, Pizzuti L, Sergi D, et al. FOLFIRI as a second-line therapy in patients with docetaxel-pretreated gastric cancer: a historical cohort. J Exp Clin Cancer Res 2013;32:67.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 152.

    Sym SJ, Ryu MH, Lee JL, et al. Salvage chemotherapy with biweekly irinotecan, plus 5-fluorouracil and leucovorin in patients with advanced gastric cancer previously treated with fluoropyrimidine, platinum, and taxane. Am J Clin Oncol 2008;31:151–156.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 153.

    Assersohn L, Brown G, Cunningham D, et al. Phase II study of irinotecan and 5-fluorouracil/leucovorin in patients with primary refractory or relapsed advanced oesophageal and gastric carcinoma. Ann Oncol 2004;15:64–69.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 154.

    Shitara K, Doi T, Dvorkin M, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2018;19:1437–1448.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 155.

    Shitara K, Doi T, Hosaka H, et al. Trifluridine/tipiracil (FTD/TPI) in patients (pts) aged ≥65 years with metastatic gastric/gastroesophageal junction cancer (mGC/mGEJC): subgroup analysis from TAGS. J Clin Oncol 2019;37(Suppl):Abstract 4037.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 156.

    Ilson DH, Tabernero J, Prokharau A, et al. Efficacy and safety of trifluridine/tipiracil treatment in patients with metastatic gastric cancer who had undergone gastrectomy: subgroup analyses of a randomized clinical trial. JAMA Oncol 2020;6:e193531.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 157.

    Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014;383:31–39.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 158.

    Ilson DH. Phase II trial of weekly irinotecan/cisplatin in advanced esophageal cancer. Oncology (Williston Park) 2004;18(Suppl 14):22–25.

  • 159.

    Sakai D, Boku N, Kodera Y, et al. An intergroup phase III trial of ramucirumab plus irinotecan in third or more line beyond progression after ramucirumab for advanced gastric cancer (RINDBeRG trial). J Clin Oncol 2018;36(Suppl):Abstract TPS4138.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 160.

    Klempner SJ, Maron SB, Chase L, et al. Initial report of second-line FOLFIRI in combination with ramucirumab in advanced gastroesophageal adenocarcinomas: a multi-institutional retrospective analysis. Oncologist 2019;24:475–482.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 161.

    Burtness B, Gibson M, Egleston B, et al. Phase II trial of docetaxel- irinotecan combination in advanced esophageal cancer. Ann Oncol 2009;20:1242–1248.

  • 162.

    Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:2509–2520.

  • 163.

    Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol 2020;38:1–10.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 164.

    Shitara K, Ajani JA, Moehler M, et al. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature 2022;603:942–948.

  • 165.

    Berton D, Banerjee SN, Curigliano G, et al. Antitumor activity of dostarlimab in patients with mismatch repair-deficient/microsatellite instability–high tumors: a combined analysis of two cohorts in the GARNET study. J Clin Oncol 2021;39(Suppl):Abstract 2564.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 166.

    Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol 2020;21:1353–1365.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 167.

    Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials. Lancet Oncol 2020;21:271–282.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 168.

    Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 2018;378:731–739.

  • 169.

    Solomon BJ, Drilon A, Lin JJ, et al. 1372P Repotrectinib in patients (pts) with NTRK fusion-positive (NTRK+) advanced solid tumors, including NSCLC: Update from the phase I/II TRIDENT-1 trial. Ann Oncol 2023;34(Suppl 2):S787–788.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 170.

    Salama AKS, Li S, Macrae ER, et al. Dabrafenib and trametinib in patients with tumors with BRAFV600E mutations: Results of the NCI-MATCH trial subprotocol H. J Clin Oncol 2020;38:3895–3904.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 171.

    Subbiah V, Wolf J, Konda B, et al. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. Lancet Oncol 2022;23:1261–1273.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 172.

    Rivera F, Romero C, Jimenez-Fonseca P, et al. Phase II study to evaluate the efficacy of trastuzumab in combination with capecitabine and oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial. Cancer Chemother Pharmacol 2019;83:1175–1181.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 173.

    Soularue E, Cohen R, Tournigand C, et al. Efficacy and safety of trastuzumab in combination with oxaliplatin and fluorouracil-based chemotherapy for patients with HER2-positive metastatic gastric and gastro-oesophageal junction adenocarcinoma patients: a retrospective study. Bull Cancer 2015;102:324–331.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 174.

    Chung HC, Bang YJ, Fuchs CS, et al. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Future Oncol 2021;17:491–501.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 175.

    Makiyama A, Sukawa Y, Kashiwada T, et al. Randomized, phase II study of trastuzumab beyond progression in patients with HER2-positive advanced gastric or gastroesophageal junction cancer: WJOG7112G (T-ACT Study). J Clin Oncol 2020;38:1919–1927.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 176.

    Janjigian YY, Kawazoe A, Yanez P, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature 2021;600:727–730.

  • 177.

    Janjigian YY, Kawazoe A, Bai Y, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet 2023;402:2197–2208.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 178.

    Rha SY, Oh DY, Yañez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2023;24:1181–1195.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 179.

    Maio M, Ascierto PA, Manzyuk L, et al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Ann Oncol 2022;33:929–938.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 180.

    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. JAMA Oncol 2018;4:e180013.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 181.

    Shitara K, Özgüroğlu M, Bang Y-J, 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;392:123–133.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 182.

    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;6:1571–1580.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 183.

    Fuchs CS, Özgüroğlu M, Bang Y-J, et al. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer 2022;25:197–206.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 184.

    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. Lancet 2021;398:27–40.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 185.

    Janjigian YY, Ajani JA, Moehler M, et al. First-line nivolumab plus chemotherapy for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 3-year follow-up of the phase III CheckMate 649 trial. J Clin Oncol 2024;42:2012–2020.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 186.

    Janjigian YY, Moehler MH, Ajani JA, et al. Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 5-year (y) follow-up results from CheckMate 649. J Clin Oncol 2025;43(Suppl):Abstract 398.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 187.

    Qiu MZ, Oh DY, Kato K, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ 2024;385:e078876.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 188.

    Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014;15:1224–1235.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 189.

    Tabernero J, Ohtsu A, Muro K, et al. Exposure-response analyses of ramucirumab from two randomized, phase III trials of second-line treatment for advanced gastric or gastroesophageal junction cancer. Mol Cancer Ther 2017;16:2215–2222.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 190.

    Fuchs CS, Shitara K, Di Bartolomeo M, et al. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2019;20:420–435.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 191.

    Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med 2020;382:2419–2430.

  • 192.

    Van Cutsem E, di Bartolomeo M, Smyth E, et al. Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study. Lancet Oncol 2023;24:744–756.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 193.

    Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol 2019;32:147–153.

  • 194.

    Okamura R, Boichard A, Kato S, et al. Analysis of NTRK alterations in pan-cancer adult and pediatric malignancies: Implications for NTRK- targeted therapeutics. JCO Precis Oncol. Published online November 15, 2018. doi:10.1200/PO.18.00183

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 195.

    Arnold A, Daum S, von Winterfeld M, et al. Analysis of NTRK expression in gastric and esophageal adenocarcinoma (AGE) with pan-TRK immunohistochemistry. Pathol Res Pract 2019;215:152662.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 196.

    Shinozaki-Ushiku A, Ishikawa S, Komura D, et al. The first case of gastric carcinoma with NTRK rearrangement: identification of a novel ATP1B-NTRK1 fusion. Gastric Cancer 2020;23:944–947.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 197.

    Hong DS, DuBois SG, Kummar S, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020;21:531–540.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 198.

    Oaknin A, Tinker AV, Gilbert L, et al. Clinical activity and safety of the anti–programmed death 1 monoclonal antibody dostarlimab for patients with recurrent or advanced mismatch repair–deficient endometrial cancer: a nonrandomized phase 1 clinical trial. JAMA Oncol 2020;6:1766–1772.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 199.

    Andre T, Berton D, Curigliano G, et al. Antitumor activity and safety of dostarlimab monotherapy in patients with mismatch repair deficient solid tumors: a nonrandomized controlled trial. JAMA Netw Open 2023;6:e2341165.

    • PubMed
    • Search Google Scholar
    • Export Citation
Copyright:
Copyright © 2025 by the National Comprehensive Cancer Network 2025
Page Numbers:
23
Article Category:
Research Article
Print Publication Date:
01 May 2025
Online Publication Date:
May 2025

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