Systematic Review and Network Meta‐Analysis of Overall Survival Comparing 3 mg/kg Ipilimumab With Alternative Therapies in the Management of Pretreated Patients With Unresectable Stage III or IV Melanoma

Objective. To compare the overall survival (OS) of patients treated with 3 mg/kg ipilimumab versus alternative systemic therapies in pretreated unresectable stage III or IV melanoma patients. Methods. A systematic literature search was performed to identify relevant randomized clinical trials. From these trials, Kaplan–Meier survival curves for each intervention were digitized and combined by means of a Bayesian network meta‐analysis (NMA) to compare different drug classes. Results. Of 38 trials identified, 15 formed one interlinked network by drug class to allow for an NMA. Ipilimumab, at a dose of 3 mg/kg, was associated with a greater mean OS time (18.8 months; 95% credible interval [CrI], 15.5–23.0 months) than single‐agent chemotherapy (12.3 months; 95% CrI, 6.3–28.0 months), chemotherapy combinations (12.2 months; 95% CrI, 7.1–23.3 months), biochemotherapies (11.9 months; 95% CrI, 7.0–22.0 months), single‐agent immunotherapy (11.1 months; 95% CrI, 8.5–16.2 months), and immunotherapy combinations (14.1 months; 95% CrI, 9.0–23.8 months). Conclusion. Results of this NMA were in line with previous findings and suggest that OS with ipilimumab is expected to be greater than with alternative systemic therapies, alone or in combination, for the management of pretreated patients with unresectable stage III or IV melanoma. 摘要 目的： 比较易普利单抗3 mg/kg与替代全身疗法治疗经治不可切除III或IV期黑色素瘤患者的总生存期（OS）。 方法： 通过系统文献检索查找相关随机临床试验。从这些试验中，将每种药物干预的Kaplan‐Meier生存曲线数字化并通过Bayesian网络荟萃分析（NMA）结合用于比较不同的药物类别。 结果： 在检索到的38项研究中，15项通过药物类别形成一个互相关联的网络进而可用来进行NMA。与单药化疗[12.3个月；95%可信区间（CrI），6.3 ~28.0个月]、联合化疗（12.2个月；95% CrI，7.1 ~23.3个月）、生物化疗（11.9个月；95% CrI，7.0 ~22.0个月）和单药免疫疗法（11.1 个月；95% CrI，8.5 ~16.2个月）和联合免疫疗法（14.1个月；95% CrI，9.0 ~23.8个月）相比，易普利单抗3 mg/kg与更长的平均OS相关（18.8个月；95% CrI，15.5 ~23.0个月）。 结论： 该NMA结果与既往的研究结果相一致，并提示易普利单抗治疗经治不可切除III或IV期黑色素瘤患者的预期OS要长于替代全身疗法（单药或联合治疗）的OS。 The overall survival of patients treated with 3 mg/kg ipilimumab was compared with those given alternative systemic therapies in pretreated unresectable stage III or IV melanoma patients. The overall survival times seen with ipilimumab are expected to be greater than those with alternative systemic therapies.