Panobinostat Plus Bortezomib Versus Lenalidomide in Patients with Relapsed and/or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Treatment Comparison of Survival Outcomes using Patient-level Data
Panobinostat Plus Bortezomib Versus Lenalidomide in Patients with Relapsed and/or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Treatment Comparison of Survival Outcomes using Patient-level Data
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帕比司他加硼替佐米与来那度胺治疗复发和/或难治性多发性骨髓瘤患者：使用患者水平数据对生存结果进行匹配调整间接治疗比较
DOI：
10.1007/s40258-016-0271-0
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发表时间：
2017
影响因子：
3.6
通讯作者：
A. Roy
中科院分区：
文献类型：
--
作者：
I. Majer;G. Wetering;Z. Polányi;A. Krishna;E. Gray;A. Roy
背景：在英国，既往接受≥2次治疗的多发性骨髓瘤患者的护理标准是来那度胺加地塞米松（LEN + DEX）和泊马度胺加地塞米松（POM + DEX）（仅在威尔士）。最近，panobinostat +硼替佐米和DEX （PAN + BTZ + DEX）在这种情况下获得许可。目前的研究评估了PAN + BTZ + DEX与LEN + DEX（主要比较物）和POM + DEX（探索性比较物）的无进展生存期（PFS）和总生存期（OS）结果。方法基于锚点的间接治疗比较不可行，采用匹配调整的间接治疗比较方法。为了比较生存结果，使用已发表的Kaplan-Meier生存估计为比较者生成患者水平的数据。PAN + BTZ + DEX的近似患者水平数据和匹配数据的使用允许使用Cox比例风险模型和比例风险假设的评估。在有证据表明违反比例风险假设的情况下，估计时间相关风险比（hr）。预测PFS和OS的中位数和平均值。结果PFS和OS均不满足比例风险假设，因此估计了随时间变化的hr。使用时间相关的HRs， PAN + BTZ + DEX的平均PFS估计为11.83个月，LEN + DEX的平均PFS估计为10.96个月。相应的平均OS估计分别为30.73和27.76个月。与POM + DEX的比较受到很大的不确定性的影响，不能做出强有力的推论。据我们所知，这是第一个将匹配调整的间接治疗比较与时间相关的HR相结合来解决HR变化模式的研究。结果表明，在多发性骨髓瘤三线治疗中，PAN + BTZ + DEX和LEN + DEX治疗与相似的平均PFS和OS相关。
BackgroundIn the UK, the standard of care for patients with multiple myeloma who received ≥2 prior treatments is lenalidomide plus dexamethasone (LEN + DEX) and pomalidomide plus DEX (POM + DEX) (in Wales only). Recently, panobinostat plus bortezomib and DEX (PAN + BTZ + DEX) was licensed in this setting. The current study assessed the progression-free survival (PFS) and overall survival (OS) outcomes with PAN + BTZ + DEX versus LEN + DEX (primary comparator) and POM + DEX (exploratory comparator).MethodsSince an anchor-based indirect treatment comparison was not feasible, the matching-adjusted indirect treatment comparison approach was used. To compare the survival outcomes, patient-level data were generated for the comparators utilizing published Kaplan–Meier survival estimates. The use of approximated patient-level data and matched data for PAN + BTZ + DEX allowed the use of Cox proportional hazards models and the assessment of the proportional hazards assumption. In cases where there was evidence that the proportional hazards assumption was violated, time-dependent hazard ratios (HRs) were estimated. Median and mean values for PFS and OS were predicted.ResultsFor both PFS and OS, the proportional hazards assumption was not satisfied, therefore time-dependent HRs were estimated. Using time-dependent HRs, the mean PFS was estimated to be 11.83 months for PAN + BTZ + DEX and 10.96 months for LEN + DEX. The corresponding mean OS estimates were 30.73 and 27.76 months, respectively. Comparisons with POM + DEX were affected by large uncertainty and did not allow making robust inferences.ConclusionsTo our knowledge, this is the first study that combined matching-adjusted indirect treatment comparison with time-dependent HRs to address changing patterns in the HR. The results suggest that treatment with PAN + BTZ + DEX and LEN + DEX are associated with similar mean PFS and OS in the third-line treatment setting of multiple myeloma.
影响因子：
20.3
作者：
Catley, Laurence;Weisberg, Ellen;Anderson, Kenneth C.
通讯作者：
Anderson, Kenneth C.
影响因子：
5
作者：
Brookhart, M. Alan;Schneeweiss, Sebastian;Sturmer, Til
通讯作者：
Sturmer, Til
影响因子：
8.9
作者：
Kumar, SK;Therneau, TM;Greipp, PR
通讯作者：
Greipp, PR