Evidera, London, UK.
Evidera, Paris, France.
Value Health. 2021 Aug;24(8):1137-1144. doi: 10.1016/j.jval.2021.03.004. Epub 2021 May 8.
Population-adjusted comparisons of progression-free survival (PFS) from single-arm trials of cancer treatments can be derived using matching-adjusted indirect comparisons (MAICs); however, results are still susceptible to bias, particularly if the trials had different tumor assessment schedules. This study aims to assess the effects of assessment-schedule matching (ASM) on the relative effectiveness on the PFS of avelumab versus approved comparator immunotherapies or chemotherapy after population matching in the second-line (2L) setting for metastatic urothelial carcinoma.
The MAIC used patient-level data for avelumab from the JAVELIN Solid Tumor trial (NCT01772004). PFS was compared with published curves for other treatments to obtain population-adjusted hazard ratios (HRs). The MAIC was repeated after conducting ASM for differences in tumor assessment scheduled first at 6 weeks for avelumab and durvalumab and at 8 or 9 weeks for other treatments.
MAIC adjustment alone altered the HR estimates up to 23%, whereas MAIC plus ASM resulted in up to 32.7% reductions from naive comparisons. Even in cases in which MAIC had little effect, ASM brought an additional change of 11.1% to 15.4%. Overall, the HR range of avelumab versus other treatments changed from 0.83 to 1.25 for naive comparisons to 0.76 to 0.99 after ASM plus MAIC, numerically favoring avelumab.
Small variations in assessment schedules can introduce bias in unanchored indirect treatment comparisons of interval-censored time-to-event outcomes. In this study, adjusted PFS was comparable across second-line urothelial carcinoma treatment options, numerically favoring avelumab versus immunotherapies and chemotherapy agents. Correcting this bias is especially important when HRs are applied in cost-effectiveness models to transition patients between states.
对于癌症治疗的单臂试验，通过匹配调整间接比较（MAIC）可以得出经过人群调整的无进展生存期（PFS）的比较；然而，结果仍然容易受到偏差的影响，特别是如果试验有不同的肿瘤评估时间表。本研究旨在评估在二线（2L）转移性尿路上皮癌人群匹配后，评估时间表匹配（ASM）对avelumab 与已批准的免疫治疗或化疗比较的 PFS 相对有效性的影响。
使用 JAVELIN 实体瘤试验（NCT01772004）中avelumab 的患者水平数据进行 MAIC。通过与其他治疗方法的已发表曲线进行比较，获得人群调整的风险比（HR），以比较 PFS。在对 6 周时avelumab 和 durvalumab 以及其他治疗 8 或 9 周时的肿瘤评估计划差异进行 ASM 后，重复 MAIC。
仅 MAIC 调整就改变了 HR 估计值高达 23%，而 MAIC 加 ASM 则使与对照相比的 HR 降低高达 32.7%。即使在 MAIC 影响不大的情况下，ASM 也会带来 11.1%至 15.4%的额外变化。总体而言，与对照相比，未经调整的 HR 范围为 avelumab 为 0.83 至 1.25，而经过 ASM 加 MAIC 后为 0.76 至 0.99，数值上有利于 avelumab。
评估时间表的微小变化会给无锚定的区间 censored 时间到事件结果的间接治疗比较引入偏差。在本研究中，二线尿路上皮癌治疗选择的调整 PFS 是可比的，数值上有利于 avelumab 与免疫治疗和化疗药物相比。当 HR 应用于成本效益模型以在状态之间转换患者时，纠正这种偏差尤为重要。
