Meta-Analysis
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2022; 14(10): 2061-2076
Published online Oct 15, 2022. doi: 10.4251/wjgo.v14.i10.2061
Combining of chemotherapy with targeted therapy for advanced biliary tract cancer: A systematic review and meta-analysis
Xue-Song Bai, Sheng-Nan Zhou, Yi-Qun Jin, Xiao-Dong He
Xue-Song Bai, Sheng-Nan Zhou, Xiao-Dong He, Department of General Surgery, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
Yi-Qun Jin, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Author contributions: Bai XS conceived the study idea; Bai XS, Zhou SN and Jin YQ conducted the literature searches and review of studies, performed data extraction, interpreted data analyses and drafted manuscripts; He XD advised on data interpretation, advised on ethodologies and helped performed statistical analysis of the manuscript; All authors interpreted data and wrote the report. All authors contributed to the article and approved the submitted version.
Supported by China Academy of Medical Science Innovation Fund for Medical Sciences, CIFMS, No. 2021-I2M-1-022-2021-S4.
Conflict-of-interest statement: All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
PRISMA 2009 Checklist statement: The guidelines of the PRISMA 2009 Statement have been adopted.
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: Xiao-Dong He, Doctor, MD, Professor, Department of General Surgery, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China. hxdpumch@163.com
Received: June 8, 2022
Peer-review started: June 8, 2022
First decision: August 20, 2022
Revised: September 4, 2022
Accepted: September 13, 2022
Article in press: September 13, 2022
Published online: October 15, 2022
Abstract
BACKGROUND

Targeted therapy (TT) has resulted in controversial efficacy as first-line treatment for biliary tract cancer (BTC). More efficacy comparisons are required to clarify the overall effects of chemotherapy (CT) combined with TT and CT alone on advanced BTC.

AIM

To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.

METHODS

The PubMed, EMBASE, ClinicalTrials, Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022. Only randomized clinical trials (RCTs) including comparisons between the combination of gemcitabine-based CT with TT and CT alone as first-line treatment for advanced BTC were eligible (PROSPERO-CRD42022313001). The odds ratios (ORs) for the objective response rate (ORR) and hazard ratios (HRs) for both progression-free survival (PFS) and overall survival (OS) were calculated and analyzed. Subgroup analyses based on different targeted agents, CT regimens and tumor locations were prespecified.

RESULTS

Nine RCTs with a total of 1361 individuals were included and analyzed. The overall analysis showed a significant improvement in ORR in patients treated with CT + TT compared to those treated with CT alone (OR = 1.43, 95%CI: 1.11-1.86, P = 0.007) but no difference in PFS or OS. Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor (OR = 1.67, 95%CI: 1.17-2.37, P = 0.004) but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor. Notably, patients who received a CT regimen of gemcitabine + oxaliplatin in the CT + TT arm had both a higher ORR (OR = 1.75, 95%CI: 1.20-2.56, P = 0.004) and longer PFS (HR = 0.83, 95%CI: 0.70-0.99, P = 0.03) than those in the CT-only arm. Moreover, patients with cholangiocarcinoma treated with CT + TT had significantly increased ORR and PFS (ORR, OR = 2.06, 95%CI: 1.27-3.35, PFS, HR = 0.79, 95%CI: 0.66-0.94).

CONCLUSION

CT + TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes, and highlighting the importance of CT regimens and tumor types in the application of TT.

Keywords: Advanced biliary tract cancer, Targeted therapy, Chemotherapy, Meta-analysis, Randomized controlled trial, First-line treatment

Core Tip: The clinical efficacy of adding targeted agents to first-line treatment of biliary tract cancer (BTC) remains unclear. Our study is the first meta-analysis of randomized clinical trials to evaluate the efficacy of the combination of targeted therapy (TT) with standard chemotherapy (CT) as first-line treatment in patients with advanced BTC. We assessed the efficacy of combined TT and CT in terms of objective response rate, progression-free survival and overall survival. Subgroup analyses were conducted based on different targeted agents, CT regimens and tumor locations.