当前位置: X-MOL 学术JAMA Oncol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The Role of Maintenance Strategies in Metastatic Colorectal Cancer: A Systematic Review and Network Meta-analysis of Randomized Clinical Trials.
JAMA Oncology ( IF 22.5 ) Pub Date : 2019-12-19 , DOI: 10.1001/jamaoncol.2019.4489
Mohamad Bassam Sonbol 1 , Luke J Mountjoy 1 , Belal Firwana 2 , Alex J Liu 1 , Diana Almader-Douglas 3 , Kabir Mody 4 , Joleen Hubbard 5 , Mitesh Borad 1 , Daniel H Ahn 1 , M Hassan Murad 6 , Tanios Bekaii-Saab 1
Affiliation  

Importance In metastatic colorectal cancer, induction combination chemotherapy with a targeted agent is considered the mainstay of treatment. Multiple randomized clinical trials have examined different strategies of continuing cytotoxic therapy until progression compared with a period of either observation or the use of various maintenance agents. However, those randomized clinical trials have shown inconsistent efficacy results that make it challenging to draw any conclusion on which strategy is preferred. Therefore, a network meta-analysis is helpful to compare different agents across randomized clinical trials. Objective To evaluate the comparative effectiveness of different treatment strategies for patients with metastatic colorectal cancer. Evidence Review MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials evaluating different strategies for patients with previously untreated metastatic colorectal cancer. Trials of interest included those including patients with metastatic colorectal cancer who were treated with an initial period of cytotoxic chemotherapy (with or without a biologic) and then switched to one of the following strategies: observation; maintenance with bevacizumab (Bev), fluoropyrimidine (FP), or both (FP + Bev); or continuing the induction regimen until progression. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian and Laird random-effects model. Network meta-analysis was conducted using a random-effects consistency model to pool evidence from direct and indirect comparisons. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Higher SUCRA scores correspond to greater efficacy. Initial analysis was performed on December 18, 2018. An updated search was performed in April 2019, and no additional studies were added. Findings Twelve trials at low risk of bias (5540 patients; age range, 23-85 years; 64.4 % male) were included. Network meta-analysis showed no benefit of continuing full cytotoxic chemotherapy until progression vs observation in terms of PFS (hazard ratio, 0.71; 95% CI, 0.46-1.09) and OS (hazard ratio, 0.95; 95% CI, 0.85-1.07). Compared with observation, maintenance therapy showed a PFS benefit (hazard ratio, 0.58; 95% CI, 0.43-0.77) but not an OS benefit (hazard ratio, 0.91; 95% CI, 0.83-1.01). All maintenance strategies (FP, FP + Bev, and Bev) showed significant improvement in PFS vs observation. On SUCRA analysis, maintenance treatment (FP or FP + Bev) had the highest likelihood of achieving improved PFS (67.1% for FP, 99.8% for FP + Bev, and 36.5% for Bev) and OS (81.3% for FP, 73.2% for FP + Bev, and 32.6% for Bev). Conclusions and Relevance For patients with metastatic colorectal cancer, there is no benefit to continuing the full induction regimen until progression, without a period of either observation or maintenance treatment. A maintenance strategy with a fluoropyrimidine, with or without the addition of bevacizumab, is preferred. However, given the lack of a clear OS benefit, shared decision-making should include observation as an acceptable alternative.

中文翻译:

维持策略在转移性结直肠癌中的作用:随机临床试验的系统评价和网络荟萃分析。

重要性在转移性大肠癌中,靶向药物的诱导联合化疗被认为是治疗的主要手段。与观察或使用各种维持剂的时期相比,多项随机临床试验已经研究了持续进行细胞毒性治疗直至进展的不同策略。但是,那些随机临床试验显示出不一致的疗效结果,因此很难就首选哪种策略得出任何结论。因此,网络荟萃分析有助于比较随机临床试验中的不同药物。目的评估不同治疗策略对转移性结直肠癌患者的比较效果。证据审查MEDLINE,Embase,Scopus,Web of Science,并在对照试验的Cochrane中央登记册中搜索随机临床试验,以评估先前未治疗的转移性结直肠癌患者的不同策略。感兴趣的试验包括那些接受转移性结直肠癌治疗的患者,这些患者接受了初期细胞毒性化学疗法(有或没有生物制剂)的治疗,然后转换为以下策略之一:用贝伐单抗(Bev),氟嘧啶(FP)或两者(FP + Bev)维持;或继续进行诱导治疗直至进展。感兴趣的结果包括总生存期(OS)和无进展生存期(PFS)。使用DerSimonian和Laird随机效应模型汇总总体效应。使用随机效应一致性模型进行网络荟萃分析,以收集来自直接和间接比较的证据。使用累积排名(SUCRA)概率下的表面对代理进行排名。较高的SUCRA分数对应较高的功效。初步分析于2018年12月18日进行.2019年4月进行了更新搜索,未添加任何其他研究。结果包括12项偏倚风险低的试验(5540例患者;年龄范围23-85岁;男性64.4%)。网络荟萃分析显示继续进行完整的细胞毒性化疗没有益处,直到就PFS(危险比,0.71; 95%CI,0.46-1.09)和OS(危险比,0.95; 95%CI,0.85-1.07)而言,直到进展与观察相比,继续进行完整的细胞毒性化疗没有益处。 。与观察相比,维持治疗显示了PFS获益(危险比,0.58; 95%CI,0.43-0。77),但没有OS收益(危险比,0.91; 95%CI,0.83-1.01)。与观察相比,所有维护策略(FP,FP + Bev和Bev)均显示出PFS的显着改善。在SUCRA分析中,维持治疗(FP或FP + Bev)实现PFS改善的可能性最大(FP为67.1%,FP + Bev为99.8%,Bev为36.5%)和OS(FP为81.3%,73.2%)对于FP + Bev,对于Bev为32.6%)。结论和相关性对于转移性结直肠癌患者,在没有观察或维持治疗的情况下,继续完整的诱导方案直至进展一直没有益处。优选在有或没有贝伐珠单抗的情况下使用氟嘧啶的维持策略。但是,由于缺乏明确的操作系统优势,因此共享决策应包括观察作为可接受的替代方案。
更新日期:2020-03-12
down
wechat
bug