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SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1570467
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
Provisionally accepted
Jiaojiao YuHua ZhuMingxu LiXiaoxia TangKe LuanYinhuan ZhiShan YinYuanqi SuJingyan LongJieru Quan
Qubo He*
Chenchen Li*- Guangxi University of Science and Technology, Liuzhou, China
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The 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).Databases 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).The 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.Neoadjuvant PD-1/PD-L1 inhibitors plus CRT have demonstrated favourable response rates and tolerable toxicity profiles for LARC.
Keywords: PD-1 inhibitor, programmed cell death protein 1 inhibitor, programmed death-ligand 1 inhibitor, rectal cancer, Neoadjuvant, Chemoradiotherapy, metaanalysis
Received: 03 Feb 2025; Accepted: 16 Apr 2025.
Copyright: © 2025 Yu, Zhu, Li, Tang, Luan, Zhi, Yin, Su, Long, Quan, He and Li. 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) or licensor 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.
* Correspondence:
Qubo He, Guangxi University of Science and Technology, Liuzhou, China
Chenchen Li, Guangxi University of Science and Technology, Liuzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.