Case Report
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2024; 30(9): 1237-1249
Published online Mar 7, 2024. doi: 10.3748/wjg.v30.i9.1237
PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma: A case report
Yue-Hong Kong, Mei-Ling Xu, Jun-Jun Zhang, Guang-Qiang Chen, Zhi-Hui Hong, Hong Zhang, Xiao-Xiao Dai, Yi-Fu Ma, Xiang-Rong Zhao, Chen-Yang Zhang, Rong-Zheng Chen, Peng-Fei Xing, Li-Yuan Zhang
Yue-Hong Kong, Mei-Ling Xu, Jun-Jun Zhang, Yi-Fu Ma, Xiang-Rong Zhao, Chen-Yang Zhang, Rong-Zheng Chen, Peng-Fei Xing, Li-Yuan Zhang, Center for Cancer Diagnosis and Treatment, The Second Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
Yue-Hong Kong, Mei-Ling Xu, Jun-Jun Zhang, Yi-Fu Ma, Xiang-Rong Zhao, Chen-Yang Zhang, Rong-Zheng Chen, Peng-Fei Xing, Li-Yuan Zhang, Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
Yue-Hong Kong, Mei-Ling Xu, Jun-Jun Zhang, Yi-Fu Ma, Xiang-Rong Zhao, Chen-Yang Zhang, Rong-Zheng Chen, Peng-Fei Xing, Li-Yuan Zhang, Institution of Radiotherapy & Oncology, Soochow University, Suzhou 215000, Jiangsu Province, China
Guang-Qiang Chen, Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
Zhi-Hui Hong, Department of Nuclear Medicine, The Second Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
Hong Zhang, Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
Xiao-Xiao Dai, Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
Co-first authors: Yue-Hong Kong and Mei-Ling Xu.
Co-corresponding authors: Peng-Fei Xing and Li-Yuan Zhang.
Author contributions: Kong YH and Xu ML contributed to study conception and design, enrolled and took care of the patient, collected clinical data, performed the experiments and analyzed the data, wrote and revised the manuscript and figure; Zhang JJ and Chen GQ enrolled and took care of the patient; Hong ZH, Zhang H, Dai XX, Ma YF, Zhao XR, Zhang CY and Chen RZ collected clinical data, performed the experiments and analyzed the data; Chen GQ and Hong ZH performed imaging analysis; Dai XX and Zhao XR conducted pathological analysis; Zhang H, Ma YF and Zhang JJ helped flow cytometry data analysis; Xing PF and Zhang LY contributed to study conception and design, project administration, funding acquisition, re-vised the manuscript and figure. Kong YH and Xu ML contributed equally to this work as co-first authors. Xing PF and Zhang LY contributed efforts of equal substance throughout the research process as co-corresponding authors, the designation of co-corresponding authorship accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resultant paper, we believe that designating Xing PF and Zhang LY as co-corresponding authors is appropriate. All authors reviewed and approved the final version of the manuscript.
Supported by the Suzhou Medical Center, No. Szlcyxzx202103; the National Natural Science Foundation of China, No. 82171828; the Key R&D Plan of Jiangsu Province (Social Development), No. BE2021652; the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University, No. XKTJHRC20210011; Wu Jieping Medical Foundation, No. 320.6750.2021-01-12; the Special Project of “Technological Innovation” Project of CNNC Medical Industry Co. Ltd, No. ZHYLTD2021001; Suzhou Science and Education Health Project, No. KJXW2021018; Foundation of Chinese Society of Clinical Oncology, No. Y-pierrefabre202102-0113; Beijing Bethune Charitable Foundation, No. STLKY0016; Research Projects of China Baoyuan Investment Co., No. 270004; Suzhou Gusu Health Talent Program, No. GSWS2022028; Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University, No. GZN1202302.
Informed consent statement: Written informed consent has been obtained from the patient to publish this paper.
Conflict-of-interest statement: Authors declare that there were no competing interests.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
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: Li-Yuan Zhang, PhD, Chief Physician, Center for Cancer Diagnosis and Treatment, The Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Suzhou 215000, Jiangsu Province, China. zhangliyuan@suda.edu.cn
Received: December 6, 2023
Peer-review started: December 6, 2023
First decision: January 4, 2024
Revised: January 6, 2024
Accepted: February 4, 2024
Article in press: February 4, 2024
Published online: March 7, 2024
Abstract
BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.

CASE SUMMARY

We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.

CONCLUSION

PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Keywords: Pancreatic ductal adenocarcinoma, PRaG 3.0 therapy, Human epidermal growth factor receptor 2, Novel combination therapy, Case report

Core Tip: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide. Herein, we present a case of multiple metastatic PDAC with immunohistochemistry (IHC) mismatch repair proficient but human epidermal growth factor receptor 2 (HER-2) IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months. We proposed that PRaG 3.0 might be a good therapeutic strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy.