Han MR, Shin JE, Lim SH, Lee J, Kim ST. Association of claudin 18.2 expression with outcomes of ramucirumab plus paclitaxel as second-line therapy in advanced gastric cancer. World J Gastrointest Oncol 2026; 18(8): 121158 [DOI: 10.4251/wjgo.v18.i8.121158]
Corresponding Author of This Article
Seung Tae Kim, PhD, Professor, Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-Gu, Seoul 06351, South Korea. shty1@skku.edu
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Oncology
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Han MR, Shin JE, Lim SH, Lee J, Kim ST. Association of claudin 18.2 expression with outcomes of ramucirumab plus paclitaxel as second-line therapy in advanced gastric cancer. World J Gastrointest Oncol 2026; 18(8): 121158 [DOI: 10.4251/wjgo.v18.i8.121158]
World J Gastrointest Oncol. Aug 15, 2026; 18(8): 121158 Published online Aug 15, 2026. doi: 10.4251/wjgo.v18.i8.121158
Association of claudin 18.2 expression with outcomes of ramucirumab plus paclitaxel as second-line therapy in advanced gastric cancer
Mi-Ran Han, Ji Eun Shin, Sung Hee Lim, Jeeyun Lee, Seung Tae Kim
Mi-Ran Han, Division of Hematology-Oncology, Department of Internal Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, South Korea
Mi-Ran Han, Ji Eun Shin, Sung Hee Lim, Jeeyun Lee, Seung Tae Kim, Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
Author contributions: Han MR designed the study and wrote the manuscript; Han MR and Shin JE performed the research; Han MR and Lim SH analyzed the data; Lee J and Kim ST supervised the study and contributed to data interpretation; Kim ST revised the manuscript critically for important intellectual content; all authors have read and approved the final manuscript.
AI contribution statement: AI tools, specifically ChatGPT, were used only for limited language refinement and assistance with formal and polite academic English expression during preparation of the response to reviewers. AI tools were not used for manuscript writing, scientific interpretation, data analysis, statistical calculations, figure generation, or study design. All statistical analyses and figures were independently performed and generated by the authors using R software. No scientific content, results, or conclusions were generated by AI.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Samsung Medical Center (No. 2026-01-003).
Informed consent statement: The requirement for informed consent was waived by the Institutional Review Board of Samsung Medical Center due to the retrospective nature of the study.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: Seung Tae Kim, PhD, Professor, Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-Gu, Seoul 06351, South Korea. shty1@skku.edu
Received: March 18, 2026 Revised: April 20, 2026 Accepted: May 13, 2026 Published online: August 15, 2026 Processing time: 142 Days and 22.7 Hours
Abstract
BACKGROUND
Ramucirumab plus paclitaxel remains the standard second-line treatment for advanced gastric cancer (AGC), despite evolving frontline therapies. However, the prognostic and predictive significance of claudin 18.2 (CLDN18.2) expression in this setting remains unclear.
AIM
To evaluate the prognostic and predictive significance of CLDN18.2 expression in patients with AGC treated with ramucirumab plus paclitaxel.
METHODS
This retrospective study included patients with AGC who underwent treatment with ramucirumab plus paclitaxel as second-line therapy between January 2023 and October 2025, and had available CLDN18.2 data. CLDN18.2 positivity was defined as membranous staining in ≥ 75% of tumor cells. Survival outcomes were analyzed using Kaplan-Meier estimates and Cox models, with restricted mean survival time applied when proportional hazards assumptions were not met.
RESULTS
Among 103 patients, 42 (40.8%) and 61 (59.2%) were CLDN18.2-positive and CLDN18.2-negative, respectively. Baseline clinical and molecular characteristics did not differ significantly between the two groups. CLDN18.2 expression status was not associated with overall survival (hazard ratio = 1.12; 95%CI: 0.67-1.86; P = 0.666). Restricted mean survival time analysis also showed comparable survival between the two groups (12.7 months vs 13.3 months; P = 0.753). Progression-free survival did not differ significantly according to CLDN18.2 expression status (hazard ratio = 1.14; 95%CI: 0.70-1.85; P = 0.595), and objective response rate did not differ significantly between the two groups (30.6% vs 35.1%; P = 0.822).
CONCLUSION
CLDN18.2 expression is not associated with outcomes of ramucirumab plus paclitaxel second-line therapy and may have limited utility for treatment selection in AGC.
Core Tip: Claudin expression is an established biomarker for targeted therapy in gastric cancer; however, its clinical relevance remains uncertain. In this retrospective study, claudin expression was not associated with survival or treatment response in patients with advanced gastric cancer who were treated with ramucirumab plus paclitaxel. These findings highlight a key distinction between intrinsic tumor biomarkers and therapies targeting the tumor microenvironment. Claudin expression should not be used to guide second-line anti-angiogenic treatments, emphasizing the need for mechanism-based biomarker selection in precision oncology.
