Evidera, London, UK.
Evidera, Montreal, QC, Canada.
Adv Ther. 2019 Sep;36(9):2327-2341. doi: 10.1007/s12325-019-01034-0. Epub 2019 Jul 26.
Complex underlying risk functions associated with immuno-oncology treatments have led to exploration of different methods (parametric survival, spline, landmark, and cure-fraction models) to estimate long-term survival outcomes. The objective of this study was to examine differences in estimated short- and long-term survival in previously treated metastatic Merkel cell carcinoma (mMCC) patients receiving avelumab, when using alternative extrapolation approaches.
Efficacy data from the phase 2 JAVELIN Merkel 200 trial (part A) with at least 12 months of follow-up were analyzed. Standard parametric survival analyses and analyses of overall survival (OS) as a function of surrogate outcomes comprised of response (landmark analyses) and progression-free survival plus post-progression survival (PFS + PPS) were used to project OS. Overall survival throughout lifetime was projected and compared with the observed OS data with at least 24 months of follow-up.
Estimated OS from all three approaches provided a good fit to the observed OS curve from at least 12 months of follow-up. However, performance compared with OS data from at least 24 months showed that the landmark approach followed by PFS + PPS provided a better fit to the data as compared to standard parametric analysis. Mean life expectancy estimated with avelumab was 2.48 years with best-fitting parametric function (a log-normal distribution), 3.15 years with the landmark approach, and 3.54 years with PFS + PPS.
Although standard parametric survival analysis may provide a good fit to short-term survival, it appears to underestimate the long-term survival benefits associated with avelumab in mMCC. Extrapolations based on surrogate outcomes of response or progression predict OS outcomes from longer follow-up better and appear to provide more clinically plausible projections.
EMD Serono Inc, Rockland, MA, a business of Merck KGaA, Darmstadt, Germany.
免疫肿瘤治疗相关的复杂潜在风险函数导致了不同方法（参数生存、样条、标志和治愈分数模型）的探索，以估计长期生存结果。本研究的目的是在接受avelumab 的既往治疗转移性 Merkel 细胞癌（mMCC）患者中，使用替代外推方法，比较短期和长期估计生存率的差异。
对至少有 12 个月随访的 JAVELIN Merkel 200 期试验（A 部分）的疗效数据进行了分析。标准参数生存分析和总体生存（OS）分析作为反应（标志分析）和无进展生存加进展后生存（PFS+PPS）的替代结果进行了分析，以预测 OS。整个生命周期的 OS 进行了预测，并与至少有 24 个月随访的观察 OS 数据进行了比较。
所有三种方法的估计 OS 与至少 12 个月随访的观察 OS 曲线拟合良好。然而，与至少 24 个月的 OS 数据进行比较表明，标志后方法加 PFS+PPS 与标准参数分析相比，对数据的拟合更好。使用 avelumab 估计的平均预期寿命为 2.48 年，最佳拟合参数函数（对数正态分布）为 3.15 年，标志方法为 3.54 年，PFS+PPS 为 3.54 年。
虽然标准参数生存分析可能对短期生存提供良好的拟合，但它似乎低估了 avelumab 在 mMCC 中与长期生存益处相关的作用。基于反应或进展的替代终点的外推可以更好地预测更长随访时间的 OS 结果，并且似乎提供了更符合临床实际的预测。
EMD Serono Inc，马萨诸塞州罗克兰，隶属于德国默克公司，达姆施塔特。
