A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma.
A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma.
复制标题
DOI：
10.1002/cam4.1001
复制
发表时间：
2017-06
期刊：
影响因子：
4
通讯作者：
de Lima Lopes G
中科院分区：
文献类型：
--
作者：
da Silveira Nogueira Lima JP;Georgieva M;Haaland B;de Lima Lopes G
免疫和BRAF靶向治疗已经改变了晚期黑色素瘤的治疗方案，使临床决策成为一项具有挑战性的任务。本贝叶斯网络荟萃分析评估了免疫疗法和靶向疗法在晚期黑色素瘤中的作用。我们从电子数据库中检索了检测免疫、BRAF或MEK靶向治疗晚期黑色素瘤的随机对照试验。贝叶斯网络模型使用总生存期（OS）的风险比（HR）、无进展生存期（PFS）、缓解率（RR）的优势比（OR）以及95%可信区间（95% CrI）和药物优于其他药物的概率来比较治疗。我们评估了PD‐L1表达对免疫治疗疗效的影响。16项研究评估了6849例患者的8种治疗方法。对于OS， BRAF - MEK联合用药和PD - 1单药排名相似，优于所有其他治疗。对于PFS， BRAF - MEK联合治疗优于所有其他选择，包括CTLA - 4 - PD - 1双阻断风险比（HR: 0.56; 95% CrI: 0.33-0.97；概率更好96.2%），而BRAF单药排名接近CTLA - 4 - PD - 1阻断。对于RR， BRAF - MEK联合治疗优于包括CTLA - 4 - PD - 1在内的所有治疗（OR: 2.78; 1.18-6.30；概率优于97.1%）。在系统评价时，没有CTLA - 4 - PD - 1阻断的OS数据，尽管PFS和RR结果表明该组合也可以带来有意义的益处。根据目前的定义，PD‐L1的表达不能为患者选择基于PD‐1的免疫治疗提供信息。BRAF - MEK组合似乎是BRAF突变患者的最佳治疗方法，而PD - 1抑制剂似乎是BRAF野生型患者的最佳治疗方法。需要更长时间的随访来确定CTLA - 4 - PD - 1阻断剂的作用。免疫治疗生物标志物仍然是一个未满足的需求。
Immune and BRAF‐targeted therapies have changed the therapeutic scenario of advanced melanoma, turning the clinical decision‐making a challenging task. This Bayesian network meta‐analysis assesses the role of immunotherapies and targeted therapies for advanced melanoma. We retrieved randomized controlled trials testing immune, BRAF‐ or MEK‐targeted therapies for advanced melanoma from electronic databases. A Bayesian network model compared therapies using hazard ratio (HR) for overall survival (OS), progression‐free survival (PFS), and odds ratio (OR) for response rate (RR), along with 95% credible intervals (95% CrI), and probabilities of drugs outperforming others. We assessed the impact of PD‐L1 expression on immunotherapy efficacy. Sixteen studies evaluating eight therapies in 6849 patients were analyzed. For OS, BRAF‐MEK combination and PD‐1 single agent ranked similarly and outperformed all other treatments. For PFS, BRAF‐MEK combination surpassed all other options, including CTLA‐4‐PD‐1 dual blockade hazard ratio (HR: 0.56; 95% CrI: 0.33–0.97; probability better 96.2%), whereas BRAF single agent ranked close to CTLA‐4‐PD‐1 blockade. For RR, BRAF‐MEK combination was superior to all treatments including CTLA‐4‐PD‐1 (OR: 2.78; 1.18–6.30; probability better 97.1%). No OS data were available for CTLA‐4‐PD‐1 blockade at the time of systematic review, although PFS and RR results suggested that this combination could also bring meaningful benefit. PD‐L1 expression, as presently defined, failed to inform patient selection to PD‐1‐based immunotherapy. BRAF‐MEK combination seemed an optimal therapy for BRAF‐mutated patients, whereas PD‐1 inhibitors seemed optimal for BRAF wild‐type patients. Longer follow‐up is needed to ascertain the role of CTLA‐4‐PD‐1 blockade. Immunotherapy biomarkers remain as an unmet need.