Abstract:
Background: Evidence comparing the efficacy of different treatments for patients with unresectable colorectal liver metastases (CRLM) receiving first-line or maintenance therapy is sparse. We aimed to assess the efficacy and safety of these treatments, with a distinct focus on evaluating first-line and maintenance treatments separately. Methods: We conducted Bayesian network meta-analyses, sourcing English-language randomized controlled trials (RCTs) published through July 2023 from databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and key conference proceedings. Phase Ⅱ or Ⅲ trials that assessed two or more therapeutic regimens were included. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), adverse events graded as 3 or above (SAE), and R0 liver resection rate. Hazards Ratios (HRs) and 95% confidence intervals (CI) were used as effect size for OS and PFS, Odds Ratios (ORs) and 95% CI were used for ORR, SAEs and R0 resection rate. Subgroup and sensitive analyses were conducted to analysis the model uncertainty (PROSPERO: CRD42023420498). Results: 56 RCTs were included (50 for first-line treatment, six for maintenance therapies), with a total of 21,323 patients. Regarding first-line, for OS, the top three mechanisms were: local treatment + single-drug chemotherapy (SingleCT), Targeted therapy (TAR)+SingleCT, and TAR + multi-drug chemotherapy (MultiCT). Resection or ablation (R/A)+SingleCT, S1, and Cetuximab + intensified fluorouracil-based combination chemotherapy (ICTFU) were identified as the best treatments. For PFS, the top three mechanisms were: Immune therapy + TAR + MultiCT, multi-targeted therapy (MultiTAR), TAR + SingleCT. The top three treatments were: Atezolizumab + Bevacizumab + fluorouracil-based combination chemotherapy (CTFU), TAS-102+bevacizumab, Bevacizumab + ICTFU. Cetuximab + CTFU was the best choice for RAS/RAF wild-type patients. Regarding maintenance treatment, Bevacizumab + SingleCT and Adavosertib were the best options for OS and PFS, respectively. For safety, MultiCT was the safest, followed by local treatment + MultiCT, TAR + MultiCT caused the most SAEs. Bevacizumab plus chemotherapy was found to be the safest among all targeted combination therapies. Conclusion: In first-line, local treatment or targeted therapsy plus chemotherapy are the best mechanisms. R/A + SingleCT or CTFU performed the best for OS, Atezolizumab + Bevacizumab + ICTFU was the best option regarding PFS. For RAS/RAF wild-type patients, Cetuximab + CTFU was the optimal option. Monotherapy may be preferred choice for maintenance treatment. Combination therapy resulted in more SAEs when compared to standard chemotherapy.
摘要:
背景:比较接受一线或维持治疗的不可切除的结直肠癌肝转移(CRLM)患者不同治疗方法的疗效的证据很少。我们旨在评估这些治疗的疗效和安全性,特别注重分别评估一线和维持治疗。方法:我们进行了贝叶斯网络荟萃分析,从包括PubMed,Embase,Cochrane图书馆,ClinicalTrials.gov,和关键会议记录。包括评估两种或两种以上治疗方案的Ⅱ期或Ⅲ期试验。主要结果是总生存期(OS)。次要结局包括无进展生存期(PFS),客观反应率(ORR),不良事件分级为3级或以上(SAE),和R0肝切除率。使用危害比(HR)和95%置信区间(CI)作为OS和PFS的效应大小,ORR使用赔率(OR)和95%CI,SAEs和R0切除率。进行亚组和敏感性分析以分析模型的不确定性(PROSPERO:CRD42023420498)。结果:纳入56项RCT(一线治疗50项,六个用于维持治疗),共有21,323名患者。关于第一行,对于操作系统,前三个机制是:局部治疗+单药化疗(SingleCT),靶向治疗(TAR)+单CT,TAR+多药化疗(MultiCT)。切除或消融术(R/A)+单CT,S1和西妥昔单抗+基于氟尿嘧啶的强化联合化疗(ICTFU)被确定为最佳治疗。对于PFS,前三种机制是:免疫治疗+TAR+MultiCT,多靶向治疗(MultiTAR),TAR+SingleCT。前三名的治疗方法是:阿替珠单抗+贝伐单抗+氟尿嘧啶联合化疗(CTFU),TAS-102+贝伐单抗,贝伐单抗+ICTFU。西妥昔单抗+CTFU是RAS/RAF野生型患者的最佳选择。关于维护处理,贝伐单抗+SingleCT和Adavosertib是OS和PFS的最佳选择,分别。为了安全,MultiCT是最安全的,其次是局部治疗+MultiCT,TAR+MultiCT引起的SAE最多。发现贝伐单抗加化疗是所有靶向联合疗法中最安全的。结论:在第一线,局部治疗或靶向治疗加化疗是最好的机制。R/A+SingleCT或CTFU在操作系统中表现最好,阿替珠单抗+贝伐单抗+ICTFU是PFS的最佳选择。对于RAS/RAF野生型患者,西妥昔单抗+CTFU是最佳选择。单一疗法可能是维持治疗的首选。与标准化疗相比,联合治疗导致更多的SAE。