Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors combined with chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis

BackgroundThe objective of this meta-analysis was to assess the effectiveness and safety of neoadjuvant PD-1/L1 inhibitors plus chemoradiotherapy(CRT) for locally advanced rectal cancer (LARC).Materials and MethodsDatabases including PubMed, Embase, Cochrane Library and Web of Science were examined...

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Main Authors: Jiaojiao Yu, Zhijing Wang, Mingxu Li, Hua Zhu, Xiaoxia Tang, Ke Luan, Yinhuan Zhi, Shan Yin, Yuanqi Su, Jingyan Long, Qubo He, Jieru Quan, Chenchen Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1570467/full
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author Jiaojiao Yu
Jiaojiao Yu
Zhijing Wang
Mingxu Li
Hua Zhu
Xiaoxia Tang
Ke Luan
Yinhuan Zhi
Shan Yin
Yuanqi Su
Jingyan Long
Qubo He
Jieru Quan
Chenchen Li
Chenchen Li
Chenchen Li
Chenchen Li
author_facet Jiaojiao Yu
Jiaojiao Yu
Zhijing Wang
Mingxu Li
Hua Zhu
Xiaoxia Tang
Ke Luan
Yinhuan Zhi
Shan Yin
Yuanqi Su
Jingyan Long
Qubo He
Jieru Quan
Chenchen Li
Chenchen Li
Chenchen Li
Chenchen Li
author_sort Jiaojiao Yu
collection DOAJ
description BackgroundThe objective of this meta-analysis was to assess the effectiveness and safety of neoadjuvant PD-1/L1 inhibitors plus chemoradiotherapy(CRT) for locally advanced rectal cancer (LARC).Materials and MethodsDatabases including PubMed, Embase, Cochrane Library and Web of Science were examined for pertinent studies. Meta-analyses were conducted on pathological complete response (pCR), clinical complete response (cCR), major pathologic response (MPR), sphincter-sparing surgery (SSS), R0 resection, surgery rate, Grade≥3 adverse events (AEs), and 3-year disease-free survival (DFS).ResultsThe combined percentages of pCR, cCR, MPR, SSS, R0 resection rate, surgery rate, and 3-year DFS were 30.8%, 20.8%, 57.6%, 70.3%, 75.8%, 83.5%, and 76%, respectively. Grade ≥3 AEs manifested in 33.9% of cases. In subgroup analysis, mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) showed 50.2% pCR and 64.7% MPR. Long-course radiotherapy (LCRT) and short-course radiotherapy (SCRT) had 39.1% and 27.1% pCR rates. The contemporaneous and sequential immuno-chemoradiotherapy subgroups had 30.8% and 30.1% pCR rates. These rates matched the 33.1% and 30% pCR rates for the PD-L1 and PD-1 inhibitor subgroups. The PD-L1 and PD-1 inhibitor categories had 20.6% and 38.8% rate of Grade ≥3AEs.ConclusionNeoadjuvant PD-1/PD-L1 inhibitors plus CRT have demonstrated favourable response rates and tolerable toxicity profiles for LARC.Systematic Review RegistrationPROSPERO (CRD42024569289) https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024569289.
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spelling doaj-art-0e20bac714f94d80b7e01c301511adb62025-08-20T03:09:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15704671570467Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors combined with chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysisJiaojiao Yu0Jiaojiao Yu1Zhijing Wang2Mingxu Li3Hua Zhu4Xiaoxia Tang5Ke Luan6Yinhuan Zhi7Shan Yin8Yuanqi Su9Jingyan Long10Qubo He11Jieru Quan12Chenchen Li13Chenchen Li14Chenchen Li15Chenchen Li16Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaDepartment of Urology, Pu’er People’s Hospital, Pu’er, Yunnan, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaThe First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaSchool of Economics and Management, Guangxi University of Science and Technology, Liuzhou, Guangxi, ChinaDepartment of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, ChinaBiomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaState Key Laboratory of Oncology in South China, Guangzhou, Guangdong, ChinaBackgroundThe objective of this meta-analysis was to assess the effectiveness and safety of neoadjuvant PD-1/L1 inhibitors plus chemoradiotherapy(CRT) for locally advanced rectal cancer (LARC).Materials and MethodsDatabases including PubMed, Embase, Cochrane Library and Web of Science were examined for pertinent studies. Meta-analyses were conducted on pathological complete response (pCR), clinical complete response (cCR), major pathologic response (MPR), sphincter-sparing surgery (SSS), R0 resection, surgery rate, Grade≥3 adverse events (AEs), and 3-year disease-free survival (DFS).ResultsThe combined percentages of pCR, cCR, MPR, SSS, R0 resection rate, surgery rate, and 3-year DFS were 30.8%, 20.8%, 57.6%, 70.3%, 75.8%, 83.5%, and 76%, respectively. Grade ≥3 AEs manifested in 33.9% of cases. In subgroup analysis, mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) showed 50.2% pCR and 64.7% MPR. Long-course radiotherapy (LCRT) and short-course radiotherapy (SCRT) had 39.1% and 27.1% pCR rates. The contemporaneous and sequential immuno-chemoradiotherapy subgroups had 30.8% and 30.1% pCR rates. These rates matched the 33.1% and 30% pCR rates for the PD-L1 and PD-1 inhibitor subgroups. The PD-L1 and PD-1 inhibitor categories had 20.6% and 38.8% rate of Grade ≥3AEs.ConclusionNeoadjuvant PD-1/PD-L1 inhibitors plus CRT have demonstrated favourable response rates and tolerable toxicity profiles for LARC.Systematic Review RegistrationPROSPERO (CRD42024569289) https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024569289.https://www.frontiersin.org/articles/10.3389/fphar.2025.1570467/fullPD-1 inhibitorprogrammed cell death protein 1 inhibitorprogrammed death-ligand 1 inhibitorrectal cancerneoadjuvantchemoradiotherapy
spellingShingle Jiaojiao Yu
Jiaojiao Yu
Zhijing Wang
Mingxu Li
Hua Zhu
Xiaoxia Tang
Ke Luan
Yinhuan Zhi
Shan Yin
Yuanqi Su
Jingyan Long
Qubo He
Jieru Quan
Chenchen Li
Chenchen Li
Chenchen Li
Chenchen Li
Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors combined with chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis
Frontiers in Pharmacology
PD-1 inhibitor
programmed cell death protein 1 inhibitor
programmed death-ligand 1 inhibitor
rectal cancer
neoadjuvant
chemoradiotherapy
title Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors combined with chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis
title_full Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors combined with chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis
title_fullStr Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors combined with chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis
title_full_unstemmed Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors combined with chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis
title_short Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors combined with chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis
title_sort efficacy and safety of neoadjuvant pd 1 inhibitors or pd l1 inhibitors combined with chemoradiotherapy for locally advanced rectal cancer a systematic review and meta analysis
topic PD-1 inhibitor
programmed cell death protein 1 inhibitor
programmed death-ligand 1 inhibitor
rectal cancer
neoadjuvant
chemoradiotherapy
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1570467/full
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