局部晚期直肠癌中使用或不使用PD-1/PD-L1抑制剂的新辅助放化疗：一项系统评价和荟萃分析
Neoadjuvant chemoradiotherapy with or without PD-1/PD-L1 inhibitors in locally advanced rectal cancer: a systematic review and meta-analysis.
作者信息
Ansab Muhammad, Razi Sepideh, Nisa Farwa, Araib Eiman, Rath Shree, Khan Iqra, Ramzan Noor Ul Huda, Dilawar Esha, Saeed Anwaar
机构信息
Faculty of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan.
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
出版信息
BMC Cancer. 2025 Jul 1;25(1):1084. doi: 10.1186/s12885-025-14482-5.
BACKGROUND
Locally advanced rectal cancer (LARC) represents a pivotal stage of rectal cancer where it is possible to completely cure the cancer before its systemic spread, thus often requiring an aggressive multimodal therapy. Recent trials suggest that programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors combined with neoadjuvant chemoradiotherapy (CRT) may improve treatment outcomes. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors when integrated into neoadjuvant CRT regimens for LARC patients.
METHODS
A systematic search of PubMed, Embase, ClinicalTrials.gov, and Cochrane Central Library was conducted up to October 11, 2024. Randomized controlled trials (RCTs) comparing neoadjuvant CRT with or without PD-1/PD-L1 inhibitors were included. The primary outcomes assessed were pathological complete response (pCR), clinical complete response (cCR), and serious adverse events (SAEs). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses were performed to explore variations in radiotherapy strategies, types of PD-1/PD-L1 inhibitors used, and mismatch repair (MMR) status.
RESULTS
Six RCTs (861 patients) met the inclusion criteria. PD-1 inhibitors significantly improved pCR rates (OR = 2.10, 95% CI: 1.32-3.32, p = 0.001), particularly with short-course radiotherapy (SCRT) and agents like Camrelizumab and Tislelizumab. However, PD-1 inhibitors did not significantly enhance cCR (OR = 1.54, 95% CI: 0.51-4.63, p = 0.44) or increase SAEs (OR = 1.08, 95% CI: 0.73-1.60). Subgroup analysis based on MMR status revealed a significantly higher pCR rate in the proficient MMR (pMMR) subgroup compared to the deficient MMR (dMMR) subgroup, although the result for dMMR was non-significant due to limited sample size and the absence of reported events.
CONCLUSIONS
The addition of PD-1 inhibitors to neoadjuvant CRT significantly improves pCR rates in LARC without increasing toxicity. These findings support their potential role in standard treatment protocols, warranting further phase III trials.
REGISTRATION NUMBER
CRD42024619949.
背景
局部晚期直肠癌（LARC）是直肠癌的一个关键阶段，在此阶段有可能在癌症发生全身扩散之前将其完全治愈，因此通常需要积极的多模式治疗。最近的试验表明，程序性细胞死亡蛋白1（PD - 1）/程序性细胞死亡配体1（PD - L1）抑制剂联合新辅助放化疗（CRT）可能改善治疗效果。本系统评价和荟萃分析旨在评估PD - 1/PD - L1抑制剂纳入LARC患者新辅助CRT方案时的疗效和安全性。
方法
截至2024年10月11日，对PubMed、Embase、ClinicalTrials.gov和Cochrane中央图书馆进行了系统检索。纳入比较新辅助CRT联合或不联合PD - 1/PD - L1抑制剂的随机对照试验（RCT）。评估的主要结局为病理完全缓解（pCR）、临床完全缓解（cCR）和严重不良事件（SAE）。采用随机效应模型计算合并比值比（OR）及95%置信区间（CI）。进行亚组分析以探讨放疗策略、所用PD - 1/PD - L1抑制剂类型及错配修复（MMR）状态的差异。
结果
六项RCT（861例患者）符合纳入标准。PD - 1抑制剂显著提高了pCR率（OR = 2.10，95% CI：1.32 - 3.32，p = 0.001），特别是在短程放疗（SCRT）以及使用卡瑞利珠单抗和替雷利珠单抗等药物时。然而，PD - 1抑制剂并未显著提高cCR（OR = 1.54，95% CI：0.51 - 4.63，p = 0.44）或增加SAE（OR = 1.08，95% CI：0.73 - 1.60）。基于MMR状态的亚组分析显示，与错配修复缺陷（dMMR）亚组相比，错配修复熟练（pMMR）亚组的pCR率显著更高，尽管由于样本量有限且未报告相关事件，dMMR亚组的结果无统计学意义。
结论
在新辅助CRT中添加PD - 1抑制剂可显著提高LARC的pCR率且不增加毒性。这些发现支持了其在标准治疗方案中的潜在作用，值得进一步开展III期试验。
注册号
CRD42024619949。
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