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The optimal first-line treatment for patients with left-sided RAS wild-type metastatic colorectal cancer: Double-drug regimen or triple-drug regimen therapy

There are many treatments for metastatic colorectal cancer (mCRC). Among them, uncertainty remains especially concerning the clinical benefit of different regimens for left-sided RAS wild-type (WT) mCRC in the triple-drug therapy era. No studies have been conducted to answer this critical clinical i...

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Autores principales: Cai, Changjing, Luo, Qingqing, Liu, Yihan, Peng, Yinghui, Zhang, Xiangyang, Jiang, Zhaohui, Feng, Ziyang, Qi, Yaru, Gao, Yan, Liu, Yongting, Liu, Ping, Chen, Yihong, Guo, Cao, Shen, Hong, Zeng, Shan, Han, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561342/
https://www.ncbi.nlm.nih.gov/pubmed/36249804
http://dx.doi.org/10.3389/fphar.2022.1015510
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author Cai, Changjing
Luo, Qingqing
Liu, Yihan
Peng, Yinghui
Zhang, Xiangyang
Jiang, Zhaohui
Feng, Ziyang
Qi, Yaru
Gao, Yan
Liu, Yongting
Liu, Ping
Chen, Yihong
Guo, Cao
Shen, Hong
Zeng, Shan
Han, Ying
author_facet Cai, Changjing
Luo, Qingqing
Liu, Yihan
Peng, Yinghui
Zhang, Xiangyang
Jiang, Zhaohui
Feng, Ziyang
Qi, Yaru
Gao, Yan
Liu, Yongting
Liu, Ping
Chen, Yihong
Guo, Cao
Shen, Hong
Zeng, Shan
Han, Ying
author_sort Cai, Changjing
collection PubMed
description There are many treatments for metastatic colorectal cancer (mCRC). Among them, uncertainty remains especially concerning the clinical benefit of different regimens for left-sided RAS wild-type (WT) mCRC in the triple-drug therapy era. No studies have been conducted to answer this critical clinical issue. We performed a comprehensive analysis of published data and real-world data. First, we conducted analyses of the published trials to show the landscape of efficacy and safety in the treatments of left-sided RAS WT mCRC. Then, we initiated a multicenter real-world study as the validation dataset. This study included six published randomized controlled trials (RCTs) and a total of 1925 patients. The double-drug regimen plus cetuximab/panitumumab (D + C/P) achieved the longest overall survival (OS) in patients with left-sided mCRC (HR = 0.74, 95%CI: 0.57–0.98), while triple-drug regimen with bevacizumab (T + B, HR = 1.1, 95%CI: 0.63–2.0), compared with double-drug with bevacizumab (D + B). The D + C/P had the highest overall response rate (ORR) in patients with left-sided mCRC (OR = 1.8, 95%CI: 0.89–3.8), while T + B (OR = 1.8, 95%CI: 0.70–4.8), compared with D + B. The multicenter real-world cohort showed the double-drug regimen plus cetuximab had longer progression-free survival (PFS) in left-sided mCRC patients than the triple-drug regimen with bevacizumab. The safety analysis showed the incidence of the adverse events (grade≥3) in the triple-drug therapy plus bevacizumab was higher than that in the double-drug therapy plus cetuximab/panitumumab. This work demonstrates the ranking of three regimens for therapeutic efficacy and safety in patients with left-sided RAS WT mCRC. The double-drug regimen plus cetuximab/panitumumab appears more effective and safer than double-drug and triple-drug based regimens with bevacizumab. Further trials and cohort analyses on this topic would increase confidence in these results.
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spelling pubmed-95613422022-10-15 The optimal first-line treatment for patients with left-sided RAS wild-type metastatic colorectal cancer: Double-drug regimen or triple-drug regimen therapy Cai, Changjing Luo, Qingqing Liu, Yihan Peng, Yinghui Zhang, Xiangyang Jiang, Zhaohui Feng, Ziyang Qi, Yaru Gao, Yan Liu, Yongting Liu, Ping Chen, Yihong Guo, Cao Shen, Hong Zeng, Shan Han, Ying Front Pharmacol Pharmacology There are many treatments for metastatic colorectal cancer (mCRC). Among them, uncertainty remains especially concerning the clinical benefit of different regimens for left-sided RAS wild-type (WT) mCRC in the triple-drug therapy era. No studies have been conducted to answer this critical clinical issue. We performed a comprehensive analysis of published data and real-world data. First, we conducted analyses of the published trials to show the landscape of efficacy and safety in the treatments of left-sided RAS WT mCRC. Then, we initiated a multicenter real-world study as the validation dataset. This study included six published randomized controlled trials (RCTs) and a total of 1925 patients. The double-drug regimen plus cetuximab/panitumumab (D + C/P) achieved the longest overall survival (OS) in patients with left-sided mCRC (HR = 0.74, 95%CI: 0.57–0.98), while triple-drug regimen with bevacizumab (T + B, HR = 1.1, 95%CI: 0.63–2.0), compared with double-drug with bevacizumab (D + B). The D + C/P had the highest overall response rate (ORR) in patients with left-sided mCRC (OR = 1.8, 95%CI: 0.89–3.8), while T + B (OR = 1.8, 95%CI: 0.70–4.8), compared with D + B. The multicenter real-world cohort showed the double-drug regimen plus cetuximab had longer progression-free survival (PFS) in left-sided mCRC patients than the triple-drug regimen with bevacizumab. The safety analysis showed the incidence of the adverse events (grade≥3) in the triple-drug therapy plus bevacizumab was higher than that in the double-drug therapy plus cetuximab/panitumumab. This work demonstrates the ranking of three regimens for therapeutic efficacy and safety in patients with left-sided RAS WT mCRC. The double-drug regimen plus cetuximab/panitumumab appears more effective and safer than double-drug and triple-drug based regimens with bevacizumab. Further trials and cohort analyses on this topic would increase confidence in these results. Frontiers Media S.A. 2022-09-30 /pmc/articles/PMC9561342/ /pubmed/36249804 http://dx.doi.org/10.3389/fphar.2022.1015510 Text en Copyright © 2022 Cai, Luo, Liu, Peng, Zhang, Jiang, Feng, Qi, Gao, Liu, Liu, Chen, Guo, Shen, Zeng and Han. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Cai, Changjing
Luo, Qingqing
Liu, Yihan
Peng, Yinghui
Zhang, Xiangyang
Jiang, Zhaohui
Feng, Ziyang
Qi, Yaru
Gao, Yan
Liu, Yongting
Liu, Ping
Chen, Yihong
Guo, Cao
Shen, Hong
Zeng, Shan
Han, Ying
The optimal first-line treatment for patients with left-sided RAS wild-type metastatic colorectal cancer: Double-drug regimen or triple-drug regimen therapy
title The optimal first-line treatment for patients with left-sided RAS wild-type metastatic colorectal cancer: Double-drug regimen or triple-drug regimen therapy
title_full The optimal first-line treatment for patients with left-sided RAS wild-type metastatic colorectal cancer: Double-drug regimen or triple-drug regimen therapy
title_fullStr The optimal first-line treatment for patients with left-sided RAS wild-type metastatic colorectal cancer: Double-drug regimen or triple-drug regimen therapy
title_full_unstemmed The optimal first-line treatment for patients with left-sided RAS wild-type metastatic colorectal cancer: Double-drug regimen or triple-drug regimen therapy
title_short The optimal first-line treatment for patients with left-sided RAS wild-type metastatic colorectal cancer: Double-drug regimen or triple-drug regimen therapy
title_sort optimal first-line treatment for patients with left-sided ras wild-type metastatic colorectal cancer: double-drug regimen or triple-drug regimen therapy
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561342/
https://www.ncbi.nlm.nih.gov/pubmed/36249804
http://dx.doi.org/10.3389/fphar.2022.1015510
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