Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer.
Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer.
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PD-1和PD-L1抑制剂联合化疗在三阴性乳腺癌随机临床试验中的疗效和安全性
DOI：
10.3389/fphar.2022.960323
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发表时间：
2022
影响因子：
5.6
通讯作者：
Wang, Jing
中科院分区：
文献类型：
--
作者：
Qi, Yihang;Zhang, Wenxiang;Jiang, Ray;Xu, Olivia;Kong, Xiangyi;Zhang, Lin;Fang, Yi;Wang, Jingping;Wang, Jing
关键词：
背景：免疫检查点抑制剂(ICIS)联合化疗(CT)是近年来探索肿瘤治疗的一种新策略，在三阴性乳腺癌(TNBC)中也得到了应用。然而，几个已发表的随机对照试验(RCT)报告了不同的结果。我们进行了这项荟萃分析，以深入了解ICIS和CT在辅助和新辅助治疗环境下联合应用于TNBC患者的有效性和安全性。方法：检索EMBASE、PubMed、Cochrane和www.Clinicaltrials.gov数据库，确定从最初到2022年5月20日的潜在合格研究。纳入已发表的针对TNBC患者的PD-1/PD-L1 ICIS结合CT的随机对照试验。结果：这项荟萃分析包括6项双盲随机对照试验，包括4,081名接受PD-1或PD-L1 ICIS+CT或安慰剂+CT治疗的TNBC患者。在新辅助治疗和辅助治疗中，联合治疗的病理完全缓解率(PCR)和无进展生存率(PFS)分别提高29%(RR=1.29；95%CI：1.17~1.41；I2=0%)和PFS(HR=0.82；95%CI：0.74~0.90；I2=0%)，尤其是在PD-L1阳性人群中(HR=0.71；95%CI：0.62~0.81；I2=13%)。两种方案的安全性均可耐受，但联合治疗将增加辅助方案中严重不良事件的风险(RR=1.33；95%可信区间1.08-1.62，I2=0%)。此外，这种组合将增加佐剂环境中任何级别的甲状腺功能减退、甲亢、肺炎和皮疹的风险，以及新辅助环境中任何级别的甲状腺功能减退、甲亢、输液相关反应和严重皮肤反应的风险。结论：这项荟萃分析显示，在新佐剂和佐剂环境中安全性事件均可耐受的TNBC患者中，PD-1/PD-L1 ICIS加CT的PFS益处显著，并证实了其PFS益处。
Background: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) is a new strategy to explore cancer treatment in recent years, and it is also practiced in triple-negative breast cancer (TNBC). However, several published randomized controlled trials (RCTs) reported heterogeneous results. We conducted this meta-analysis to yield insights into the efficacy and safety of the combination of ICIs and CT for TNBC patients in both the adjuvant and neoadjuvant settings. Method: EMBASE, PUBMED, Cochrane, and www.clinicaltrials.gov databases were searched to determine potential eligible studies from the inception to 20 May 2022. Published RCTs on PD-1/PD-L1 ICIs combined with CT for TNBC patients were included. Result: This meta-analysis included six double-blind RCTs comprising 4,081 TNBC patients treated with PD-1 or PD-L1 ICIs plus CT or placebo plus CT. The combination strategy benefited a better pathologic complete response (pCR) by 29% (RR = 1.29; 95% CI: 1.17–1.41; I2 = 0%) and a better progression-free survival (PFS) (HR = 0.82; 95% CI: 0.74–0.90; I2 = 0%) in the neoadjuvant and the adjuvant settings, respectively, especially in PD-L1-positive population (HR = 0.71; 95% CI: 0.62–0.81; I2 = 13%). The safety profiles were generally tolerable in both settings but the combination treatment will increase the risk of severe adverse events in the adjuvant setting (RR = 1.33; 95% CI 1.08–1.62, I2 = 0%). Additionally, the combination will increase the risk of any-grade hypothyroidism, hyperthyroidism, pneumonia, and rash in the adjuvant setting, and the risk of any-grade hypothyroidism, hyperthyroidism, infusion-related reactions, and severe cutaneous reactions in the neoadjuvant setting. Conclusion: This meta-analysis demonstrated a significant pCR benefit and confirms the PFS benefit with PD-1/PD-L1 ICIs plus CT in TNBC patients with tolerable safety events in both neoadjuvant and adjuvant settings.
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影响因子：
158.5
作者：
Larkin, J.;Chiarion-Sileni, V.;Wolchok, J. D.
通讯作者：
Wolchok, J. D.
影响因子：
50.5
作者：
Emens, L. A.;Adams, S.;Schmid, P.
通讯作者：
Schmid, P.
影响因子：
4.6
作者：
Ghebeh H;Al-Sayed A;Eiada R;Cabangon L;Ajarim D;Suleman K;Tulbah A;Al-Tweigeri T
通讯作者：
Al-Tweigeri T
影响因子：
168.9
作者：
Cortes, Javier;Cescon, David W.;Schmid, Peter
通讯作者：
Schmid, Peter
影响因子：
50.5
作者：
Adams, S.;Dieras, V.;Schmid, P.
通讯作者：
Schmid, P.