Quinn Casey, Ma Qiufei, Kudlac Amber, Palmer Stephen, Barber Beth, Zhao Zhongyun
PRMA Consulting Ltd, Fleet, Hampshire, UK.
Amgen Inc., Thousand Oaks, CA, USA.
Adv Ther. 2016 Apr;33(4):643-57. doi: 10.1007/s12325-016-0313-x. Epub 2016 Mar 15.
Few randomized controlled trials have compared new treatments for metastatic melanoma. We sought to examine the relative treatment effect of talimogene laherparepvec compared with ipilimumab and vemurafenib.
A systematic literature review of treatments for metastatic melanoma was undertaken but a valid network of evidence could not be established because of a lack of comparative data or studies with sufficient common comparators. A conventional adjusted indirect treatment comparison via network meta-analysis was, therefore, not feasible. Instead, a meta-analysis of absolute efficacy was undertaken, adjusting overall survival (OS) data for differences in prognostic factors between studies using a published algorithm.
Four trials were included in the final indirect treatment comparison: two of ipilimumab, one of vemurafenib, and one of talimogene laherparepvec. Median OS for ipilimumab and vemurafenib increased significantly when adjustment was applied, demonstrating that variation in disease and patient characteristics was biasing OS estimates; adjusting for this made the survival data more comparable. For both ipilimumab and vemurafenib, the adjustments improved Kaplan-Meier OS curves; the observed talimogene laherparepvec OS curve remained above the adjusted OS curves for ipilimumab and vemurafenib, showing that long-term survival could differ from the observed medians.
Even with limited data, talimogene laherparepvec, ipilimumab, and vemurafenib could be compared following adjustments, thereby providing a more reliable understanding of the relative effect of treatment on survival in a more comparable patient population. The results of this analysis suggest that OS with talimogene laherparepvec is at least as good as with ipilimumab and vemurafenib and improvement was more pronounced in patients with no bone, brain, lung or other visceral metastases.
Amgen Inc.
很少有随机对照试验比较转移性黑色素瘤的新疗法。我们试图研究talimogene laherparepvec与伊匹单抗和威罗菲尼相比的相对治疗效果。
对转移性黑色素瘤的治疗进行了系统的文献综述，但由于缺乏比较数据或没有足够共同对照的研究，未能建立有效的证据网络。因此，通过网络荟萃分析进行传统的调整间接治疗比较并不可行。取而代之的是，进行了绝对疗效的荟萃分析，使用已发表的算法对研究之间预后因素的差异调整总生存（OS）数据。
最终的间接治疗比较纳入了四项试验：两项关于伊匹单抗，一项关于威罗菲尼，一项关于talimogene laherparepvec。应用调整后，伊匹单抗和威罗菲尼的中位OS显著增加，表明疾病和患者特征的差异使OS估计产生偏差；对此进行调整使生存数据更具可比性。对于伊匹单抗和威罗菲尼，调整均改善了Kaplan-Meier OS曲线；观察到的talimogene laherparepvec OS曲线仍高于伊匹单抗和威罗菲尼的调整后OS曲线，表明长期生存可能与观察到的中位数不同。
即使数据有限，调整后仍可比较talimogene laherparepvec、伊匹单抗和威罗菲尼，从而在更具可比性的患者群体中更可靠地了解治疗对生存的相对效果。该分析结果表明，talimogene laherparepvec的OS至少与伊匹单抗和威罗菲尼相当，且在无骨、脑、肺或其他内脏转移的患者中改善更为明显。
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