Although combination therapy is not recommended in patients with gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs), this strategy is widely used in clinical practice. This network meta-analysis of randomized trials evaluates targeted therapies and somatostatin analogues in GEP-advanced NETs, either alone or in combination, comparing the efficacy of different, single or combined treatment strategies in terms of progression-free survival (PFS). Interventions were grouped as analogs, everolimus, everolimus plus SSAs, sunitinib and placebo. In a secondary analysis, we also assessed the efficacy of individual-specific pharmacological treatments vs placebo or each other. From 83 studies identified, 8 randomized controlled trials were selected, with a total of 1849 patients with either functioning or non-functioning NETs. The analysis confirmed the superiority of all treatments over placebo (HR ranging from 0.34, 95% CI: 0.24-0.37 with the combination of everolimus plus SSAs to 0.42, 0.31-0.57 with the analogs; moderate quality of evidence). On ranking analysis, the combination of everolimus plus SSA (P score = 0.86) and then everolimus alone (P score = 0.65) ranked highest in increasing PFS. On comparative evaluation of different interventions, pasireotide (P score = 0.96) and everolimus + octreotide (P score = 0.82) ranked as the best pharmacological treatment options. Our findings support the use of combination therapy in the treatment of functioning and non-functioning GEP NETs. The role of pasireotide should be explored in selected subgroups of patients. Lastly, the combination of everolimus and octreotide appears promising and should be more widely considered in clinical practice.

中文翻译：

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NETs 中的靶向治疗加生长抑素类似物：网络荟萃分析。

尽管不建议对胃肠胰 (GEP) 神经内分泌肿瘤 (NETs) 患者进行联合治疗，但该策略已广泛用于临床实践。这项随机试验的网络荟萃分析评估了 GEP 高级 NETs 中的靶向治疗和生长抑素类似物，无论是单独还是联合，比较不同、单一或联合治疗策略在无进展生存期 (PFS) 方面的功效。干预措施分为类似物、依维莫司、依维莫司加 SSA、舒尼替尼和安慰剂。在二次分析中，我们还评估了个体特异性药物治疗与安慰剂或彼此的疗效。从确定的 83 项研究中，选择了 8 项随机对照试验，共有 1849 名患有功能性或非功能性 NET 的患者。分析证实所有治疗均优于安慰剂（依维莫司联合 SSA 的 HR 范围从 0.34、95% CI：0.24-0.37 到类似物的 0.42、0.31-0.57；证据质量中等）。在排名分析中，依维莫司联合 SSA（P 得分 = 0.86）和单独依维莫司（P 得分 = 0.65）在增加 PFS 方面排名最高。在对不同干预措施的比较评估中，帕瑞肽（P 评分 = 0.96）和依维莫司 + 奥曲肽（P 评分 = 0.82）被列为最佳药物治疗方案。我们的研究结果支持使用联合疗法治疗功能性和非功能性 GEP NET。应在选定的患者亚组中探索帕瑞肽的作用。最后，