Neoadjuvant Chemotherapy for Gastric Cancer - Evolving Approaches and Supporting Evidence

Sep 23, 2026

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Neoadjuvant and perioperative therapy have become promising strategies for locally advanced gastric cancer. Landmark phase III trials, including PRODIGY and RESOLVE, support neoadjuvant chemotherapy as a viable option, particularly in Asia, while the MATTERHORN trial explores perioperative immune checkpoint inhibitors. The review also evaluates Asian use of fluorouracil, leucovorin, oxaliplatin, and docetaxel in light of regional standards and toxicity concerns such as neutropenia. It highlights key issues: response assessment, limits of pathological response as a surrogate endpoint, biomarker-driven patient selection, and how long postoperative therapy should continue. It emphasizes personalization using clinical stage, pathological response, and circulating tumor DNA.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

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Abstract

Introduction

Perioperative and adjuvant strategies in Western regions

Perioperative and postoperative strategies in Asia

Rationale for neoadjuvant therapy

J Gastric Cancer. 2026 Jan;26(1):106-126 [https://doi.org/10.5230/jgc.2026.26.e2](https://doi.org/10.5230/jgc.2026.26.e2)[ ](https://doi.org/10.5230/jgc.2026.26.e2)pISSN 2093-582X·eISSN 2093-5641 Review Article Received: Sep 20, 2025 Revised: Nov 21, 2025 Accepted: Nov 21, 2025 Published online: Dec 18, 2025 Correspondence to Hyung-Don Kim Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. Email: [kimhdmd@amc.seoul.kr](kimhdmd@amc.seoul.kr) Copyright © 2026. Korean Gastric Cancer Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://](https://)[ ](https://)[creativecommons.org/licenses/by-nc/4.0](creativecommons.org/licenses/by-nc/4.0)) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ORCID iDs Hyung-Don Kim [https://orcid.org/0000-0001-9959-0642](https://orcid.org/0000-0001-9959-0642)[ ](https://orcid.org/0000-0001-9959-0642)[Min-Hee Ryu](Min-Hee Ryu) [https://orcid.org/0000-0002-1033-1263](https://orcid.org/0000-0002-1033-1263) Conflict of Interest None directly related to this work. Outside of this study, MHR received honoraria from DAEHWA Pharmaceutical, Bristol Myers Squibb, Lilly, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Novartis, Daiichi Sankyo, and AstraZeneca, and served as a consultant for DAEHWA Pharmaceutical, Bristol Myers Squibb, Lilly, and Ono Pharmaceutical. HDK received research grants from Roche/ Genentech, Amgen, and AstraZeneca, as Neoadjuvant Chemotherapy for Gastric Cancer: Evolving Approaches and Supporting Evidence Young Jae Kim, Hyung-Don Kim , Jaewon Hyung, Min-Hee Ryu Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea ABSTRACT Neoadjuvant and perioperative therapy have emerged as promising strategies for managing locally advanced gastric cancer (LAGC). Landmark phase III studies, such as PRODIGY and RESOLVE, have established neoadjuvant chemotherapy as a viable therapeutic option in Asia. More recently, the MATTERHORN trial demonstrated the potential of incorporating immune checkpoint inhibitors (ICIs) into perioperative treatment. However, the use of fluorouracil, leucovorin, oxaliplatin, and docetaxel in Asian populations warrants careful consideration, given regional treatment standards and concerns regarding chemotherapyrelated toxicities, including neutropenia. This review summarizes key perioperative trials and highlights the evolving role ofICIs while also addressing emerging evidence on targeted therapies in LAGC. Key considerations include assessment of treatment response, as the validity of pathological response as a surrogate endpoint for survival remains unclear; riskand biomarker-driven patient selection; and unresolved questions regarding the necessity and optimal duration of postoperative therapy. Personalizing postoperative treatment based on prognostic and molecular markers—including clinical stage, pathological response, and circulating tumor DNA status—represents an important next step toward improving outcomes. Keywords: Stomach neoplasms; Neoadjuvant therapy; Immunotherapy; Molecular targeted therapy INTRODUCTION Gastric cancer is the fifth most common malignancy worldwide and a major cause of cancerrelated mortality, accounting for more than 600,000 deaths annually [1,2]. In patients with locally advanced gastric cancer (LAGC), surgical resection remains the primary curative approach; however, the high rate of postoperative recurrence has prompted the development of perioperative and adjuvant strategies to improve survival. Historically, treatment approaches for LAGC have differed between Western and Asian countries. In Western regions, perioperative chemotherapy became the standard following the MAGIC and FLOT4 trial

FAQs

What is the main clinical role of neoadjuvant therapy in locally advanced gastric cancer?

Neoadjuvant therapy is presented as a promising strategy to improve outcomes and treatment compliance by enabling earlier chemotherapy delivery at relatively high dose intensity.

Which major trials are highlighted for neoadjuvant chemotherapy and perioperative approaches?

The review cites phase III PRODIGY and RESOLVE for establishing neoadjuvant chemotherapy as a viable option, and MATTERHORN for the potential integration of immune checkpoint inhibitors into perioperative treatment.

Why is chemotherapy regimen selection cautioned in Asian populations?

The review emphasizes careful consideration of fluorouracil, leucovorin, oxaliplatin, and docetaxel use due to regional treatment standards and concerns about chemotherapy-related toxicities, including neutropenia.

Sep 23, 2026

Uploaded by Himbo