Abstract：
OBJECTIVE: The safety profile of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors when associated with chemotherapy for the treatment of patients with extensive-stage small-cell lung cancer is still not fully unraveled.
METHODS: We performed a comprehensive searrch of the PubMed, Embase, and Cochrane databases for randomized controlled trials that investigated the addition of PD-1 or PD-L1 inhibitors to standard investigator choice chemotherapy. We used risk -ratios (RRs) with 95% confidence intervals (CIs) for all endpoints.
RESULTS: Six studies and 2,995 patients were included. At the baseline, the median age of the patients varied from 62 to 65 years, 311 (10.4%) had brain metastases, and 1,060 (35.4%) had liver metastases. PD-1/PD-L1 inhibitors were found to reduce fatal toxicities-related mortality (RR: 0.85; 95% CI: 0.80-0.91; p < 0.001; I2 = 49%). The intervention group had a higher incidence of decreased appetite (RR: 1.19; 95% CI: 1.02-1.40; p = 0.03; I2 = 0%), hyponatremia (RR: 1.51; 95% CI: 1.08-2.12; p = 0.02; I2 = 0%), and hypothyroidism (RR: 3.14; 95% CI: 1.10-8.95; p = 0.03; I2 = 81%) of any grade. Regarding adverse events of grade 3-4, there was no association of the addition of PD-1/PD-L1 inhibitors with an increased occurrence of any of the evaluated outcomes.
CONCLUSIONS: In this systematic review and meta-analysis, the incorporation of PD-1/PD-L1 inhibitors to chemotherapy demonstrated an excellent safety profile and to be a promising prospect for reshaping the established treatment paradigms for patients with extensive-stage small cell lung cancer.
METHODS: We performed a comprehensive searrch of the PubMed, Embase, and Cochrane databases for randomized controlled trials that investigated the addition of PD-1 or PD-L1 inhibitors to standard investigator choice chemotherapy. We used risk -ratios (RRs) with 95% confidence intervals (CIs) for all endpoints.
RESULTS: Six studies and 2,995 patients were included. At the baseline, the median age of the patients varied from 62 to 65 years, 311 (10.4%) had brain metastases, and 1,060 (35.4%) had liver metastases. PD-1/PD-L1 inhibitors were found to reduce fatal toxicities-related mortality (RR: 0.85; 95% CI: 0.80-0.91; p < 0.001; I2 = 49%). The intervention group had a higher incidence of decreased appetite (RR: 1.19; 95% CI: 1.02-1.40; p = 0.03; I2 = 0%), hyponatremia (RR: 1.51; 95% CI: 1.08-2.12; p = 0.02; I2 = 0%), and hypothyroidism (RR: 3.14; 95% CI: 1.10-8.95; p = 0.03; I2 = 81%) of any grade. Regarding adverse events of grade 3-4, there was no association of the addition of PD-1/PD-L1 inhibitors with an increased occurrence of any of the evaluated outcomes.
CONCLUSIONS: In this systematic review and meta-analysis, the incorporation of PD-1/PD-L1 inhibitors to chemotherapy demonstrated an excellent safety profile and to be a promising prospect for reshaping the established treatment paradigms for patients with extensive-stage small cell lung cancer.
摘要：
目的：程序性细胞死亡1（PD-1）/程序性细胞死亡配体1（PD-L1）抑制剂与化疗联合治疗广泛期小细胞肺癌患者的安全性仍未完全阐明。
方法：我们对PubMed进行了全面的搜索，Embase,和Cochrane数据库，用于研究在标准研究者选择化疗中添加PD-1或PD-L1抑制剂的随机对照试验。我们对所有终点使用了95%置信区间(CI)的风险比(RR)。
结果：纳入了6项研究和2,995名患者。在基线，患者的中位年龄从62岁到65岁不等，311（10.4%）有脑转移，1,060（35.4％）有肝转移。发现PD-1/PD-L1抑制剂可降低致命毒性相关的死亡率（RR：0.85；95％CI：0.80-0.91；p<0.001；I2=49％）。干预组食欲下降的发生率较高(RR:1.19;95%CI:1.02-1.40;p=0.03;I2=0%),低钠血症(RR:1.51;95%CI:1.08-2.12;p=0.02;I2=0%),和甲状腺功能减退（RR：3.14;95％CI：1.10-8.95;p=0.03;I2=81％）。关于3-4级不良事件，添加PD-1/PD-L1抑制剂与任何评估结果的发生率增加没有关联。
结论：在本系统综述和荟萃分析中，在化疗中加入PD-1/PD-L1抑制剂证明了良好的安全性,并且是重塑广泛期小细胞肺癌患者既定治疗模式的有希望的前景.
方法：我们对PubMed进行了全面的搜索，Embase,和Cochrane数据库，用于研究在标准研究者选择化疗中添加PD-1或PD-L1抑制剂的随机对照试验。我们对所有终点使用了95%置信区间(CI)的风险比(RR)。
结果：纳入了6项研究和2,995名患者。在基线，患者的中位年龄从62岁到65岁不等，311（10.4%）有脑转移，1,060（35.4％）有肝转移。发现PD-1/PD-L1抑制剂可降低致命毒性相关的死亡率（RR：0.85；95％CI：0.80-0.91；p<0.001；I2=49％）。干预组食欲下降的发生率较高(RR:1.19;95%CI:1.02-1.40;p=0.03;I2=0%),低钠血症(RR:1.51;95%CI:1.08-2.12;p=0.02;I2=0%),和甲状腺功能减退（RR：3.14;95％CI：1.10-8.95;p=0.03;I2=81％）。关于3-4级不良事件，添加PD-1/PD-L1抑制剂与任何评估结果的发生率增加没有关联。
结论：在本系统综述和荟萃分析中，在化疗中加入PD-1/PD-L1抑制剂证明了良好的安全性,并且是重塑广泛期小细胞肺癌患者既定治疗模式的有希望的前景.
