背景:免疫疗法已成为转移性去势抵抗性前列腺癌(mCRPC)的潜在治疗方法。然而,目前尚不清楚在大规模样本中确定免疫治疗的有效性和安全性.我们对mCRPC中7项III期随机试验和3项II期试验进行了荟萃分析,比较了免疫治疗与安慰剂。
方法:搜索PubMed,临床试验和Cochrane图书馆,已完成III/IV期试验.根据PRISMA声明进行数据提取。测量的结果是OS,PFS,ORR和AE。根据III期随机试验的结果,确定了3个具有结果的II期试验。
结果:共有4185例患者可用于OS评估,和3320为PFS。与安慰剂相比,免疫疗法不能改善OS(HR=0.90;95CI0.79-1.03;p=0.13).然而,免疫疗法,与安慰剂相比,尤其是ICB能够将进展风险降低18%(HR=0.82;95CI0.68~1.00;p=0.04).在接受ICBs治疗的患者中发现ORR显着改善(RR=1.90;95CI1.30-2.78;p<0.001)。免疫疗法(OR=1.01,95%CI=0.40-2.56;OR=1.27,95%CI=0.72-2.25)与任何等级的TRAE和3-4等级的TRAE均无显著相关性。然而,在亚组分析中,ICB(OR=2.85,95%CI=2.27-3.57)和疫苗(OR=0.78,95%CI=0.64-0.53)分别与显著的3-4级TRAE相关。此外,单独使用ICB可诱导PSA阳性反应[OR=2.43(1.09-5.43),P=0.03(I2=0%,P=0.83)],并且基于关于ICB的三项II期临床试验,即使没有经典疗法,在晚期PC中也有效。
结论:免疫疗法不能改善OS,但显着改善PFS和ORR,尤其是在ICBs治疗中。免疫疗法与显著的TRAE无关。然而,在亚组分析中,ICB和疫苗与显著的3-4级TRAE相关。
BACKGROUND: Immunotherapies have emerged as potential treatments for metastatic castration-resistant prostate cancer (mCRPC). However, it is still unclear to identify the efficacy and safety of immunotherapy in large-scale samples. We performed a meta-analysis of 7 phase III randomized trials and 3 phase II trials comparing immunotherapy to placebo in mCRPC.
METHODS: Searching the PubMed, ClinicalTrials and Cochrane Library, completed III/IV phase trials were identified. Data extraction was conducted according to the PRISMA statement. The measured outcomes were OS, PFS, ORR and AE. Based on the results of phase III randomized trials, 3 II phase trials with results were identified.
RESULTS: A total of 4185 patients were available for evaluation of OS, and 3320 for PFS. Compared to placebo, immunotherapies were not able to improve OS (HR = 0.90; 95%CI 0.79-1.03; p = 0.13). However, immunotherapies, especially
ICBs were able to decrease the risk of progression over placebo by 18% (HR = 0.82; 95%CI 0.68-1.00; p = 0.04). Significant ORR improvement was found in patients treated in
ICBs (RR = 1.90; 95%CI 1.30-2.78; p < 0.001). Immunotherapies (OR = 1.01, 95% CI = 0.40-2.56; OR = 1.27, 95% CI = 0.72-2.25) were not associated with significant any grade TRAEs and 3-4 grade TRAEs. However, in subgroup analysis,
ICBs (OR = 2.85, 95% CI = 2.27-3.57) and vaccines (OR = 0.78, 95% CI = 0.64-0.53) were associated with significant 3-4 grade TRAEs respectively. Moreover,
ICBs alone induced positive PSA response [OR = 2.43(1.09-5.43), P = 0.03(I2 = 0%, P = 0.83)] and was effective in advanced PC even without classical therapies based on three phase II clinical trials about ICBs.
CONCLUSIONS: Immunotherapies are not able to improve OS, but significantly improve PFS and ORR especially in ICBs treatment. Immunotherapies were not associated with significant TRAEs. However, in subgroup analysis,
ICBs and vaccines were associated with significant 3-4 grade TRAEs.