Pernomian LS, Teixeira MF, Araujo RL, Serrano Uson Junior PL. Perioperative immunotherapy in gastric cancer in the spotlight. World J Clin Oncol 2025; 16(12): 110988 [DOI: 10.5306/wjco.v16.i12.110988]
Corresponding Author of This Article
Raphael LC Araujo, MD, PhD, FACS, Department of Surgery, Carolinas Medical Center, Atrium Health, 1025 Morehead Medical Drive, Charlotte, NC 28204, United States. raphael.l.c.araujo@gmail.com
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Oncology
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 24, 2025 (publication date) through Dec 29, 2025
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World Journal of Clinical Oncology
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Pernomian LS, Teixeira MF, Araujo RL, Serrano Uson Junior PL. Perioperative immunotherapy in gastric cancer in the spotlight. World J Clin Oncol 2025; 16(12): 110988 [DOI: 10.5306/wjco.v16.i12.110988]
World J Clin Oncol. Dec 24, 2025; 16(12): 110988 Published online Dec 24, 2025. doi: 10.5306/wjco.v16.i12.110988
Perioperative immunotherapy in gastric cancer in the spotlight
Laura S Pernomian, Maria Fernanda Teixeira, Raphael LC Araujo, Pedro Luiz Serrano Uson Junior
Laura S Pernomian, Maria Fernanda Teixeira, Pedro Luiz Serrano Uson Junior, Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
Raphael LC Araujo, Department of Surgery, Carolinas Medical Center, Atrium Health, Charlotte, NC 28204, United States
Raphael LC Araujo, Department of Surgery, Universidade Federal de São Paulo, São Paulo 04024-002, Brazil
Author contributions: Pernomian LS, Teixeira MF, Araujo RL, and Serrano Uson Junior PL designed the study; Pernomian LS and Teixeira MF wrote the manuscript; and all authors revised and approved the final version.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Raphael LC Araujo, MD, PhD, FACS, Department of Surgery, Carolinas Medical Center, Atrium Health, 1025 Morehead Medical Drive, Charlotte, NC 28204, United States. raphael.l.c.araujo@gmail.com
Received: June 23, 2025 Revised: July 27, 2025 Accepted: November 14, 2025 Published online: December 24, 2025 Processing time: 186 Days and 19.4 Hours
Abstract
Perioperative fluorouracil, leucovorin, oxaliplatin and docetaxel is currently the standard chemotherapy for resectable gastric and gastroesophageal junction adenocarcinomas, based on the results of FLOT4 and ESOPEC trials. This regimen has demonstrated efficacy in tumor downstaging, enhancing the chances of curative resection, and ultimately improving the overall survival. However, despite these advances, the complete response rate in the perioperative setting remains below 10% to 15%, highlighting the need for more effective treatment strategies. Recent studies evaluating immunotherapy, such as the KEYNOTE-585 trial with pembrolizumab and the MATTERHORN trial with durvalumab, have shown promising preliminary results, including improved response rates and event-free survival. Nevertheless, these regimens are not yet considered the standard of care. This article explores the current landscape of perioperative treatments for gastric cancer and discusses future directions in this field.
Core Tip: Immunotherapy is reshaping the treatment landscape for resectable gastric and gastroesophageal junction cancers. Despite the established benefit of perioperative leucovorin, oxaliplatin, and docetaxel chemotherapy, complete pathological response rates remain below 15%. Recent phase III trials, including KEYNOTE-585 with pembrolizumab and MATTERHORN with durvalumab, have demonstrated improved pathological responses and event-free survival, particularly in biomarker-enriched subgroups such as microsatellite instability-high or programmed death-ligand 1-positive tumors. This article summarizes the evolving evidence supporting immune checkpoint inhibitors in the perioperative setting and highlights future directions toward biomarker-driven, personalized multimodal therapy for gastric cancer.
