Bristol Myers Squibb Co, Princeton, New Jersey, USA
Bristol Myers Squibb Co, Princeton, New Jersey, USA.
J Immunother Cancer. 2021 Feb;9(2). doi: 10.1136/jitc-2020-001177.
We explored whether the effectiveness of immune checkpoint inhibitors (ICIs) can be characterized by incorporating a composite of duration of response (DOR) to complement traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria for objective response rate (ORR) in an intent-to-treat (ITT) population. Furthermore, the correlation of this novel endpoint, characterized by the restricted mean time in response (RMTR), with overall survival (OS) will be examined.
We analyzed ORR alone or in combination with DOR (RMTR) in available phase I, II, and III trials evaluating nivolumab monotherapy or in combination with ipilimumab across solid tumor types. ORR was evaluated per RECIST V.1.1. DOR was estimated using individual patient data in ITT populations regardless of RECIST response, with non-responders imputed as zero. Associations between ORR alone or RMTR and OS were evaluated in the ITT population. DOR curves were generated using the Kaplan-Meier product limit method, and 6-month RMTR, a measure of response durability, was derived from the area under the curves. For ORR and RMTR in the ITT population, the strength of association with OS was analyzed using Pearson correlation coefficients ().
Nivolumab treatment was associated with longer response durations than active control in responder and ITT populations. Similarly, ORR and RMTR were both significantly correlated with OS (ORR vs OS: =0.684, p=0.02; RMTR vs OS: =0.695, p=0.018).
Combining ORR and DOR (RMTR) to objectively characterize tumor shrinkage in an ITT patient population is a novel approach that appears to correlate well with OS in patients treated with nivolumab monotherapy or in combination with ipilimumab. This endpoint may provide a more complete characterization of tumor shrinkage to incorporate into the design of future ICI clinical trials. However, confirmation of this approach will require further research.
我们探索了将免疫检查点抑制剂（ICI）的疗效通过纳入缓解持续时间（DOR）的综合指标来描述，以补充客观缓解率（ORR）的实体瘤反应评估标准（RECIST）标准，用于意向治疗（ITT）人群。此外，将通过受限平均反应时间（RMTR）来描述的这一新的终点与总生存期（OS）之间的相关性进行检验。
我们分析了在评估nivolumab 单药或联合 ipilimumab 的各种 I 期、II 期和 III 期临床试验中，ORR 单独或与 DOR（RMTR）联合在ITT 人群中的疗效。ORR 按照 RECIST V.1.1 进行评估。DOR 使用 ITT 人群中患者的个体数据进行估计，无论 RECIST 反应如何，无反应者都被假定为零。在 ITT 人群中评估 ORR 单独或 RMTR 与 OS 之间的相关性。使用 Kaplan-Meier 乘积限法生成 DOR 曲线，并从曲线下面积推导出 6 个月 RMTR，这是反应耐久性的度量。对于 ITT 人群中的 ORR 和 RMTR，使用 Pearson 相关系数（）分析与 OS 关联的强度。
与活性对照组相比，nivolumab 治疗在反应者和 ITT 人群中均具有更长的缓解持续时间。同样，ORR 和 RMTR 均与 OS 显著相关（ORR 与 OS：=0.684，p=0.02；RMTR 与 OS：=0.695，p=0.018）。
将 ORR 和 DOR（RMTR）相结合，客观地描述 ITT 患者人群中的肿瘤缩小是一种新方法，与 nivolumab 单药或联合 ipilimumab 治疗的患者的 OS 相关性良好。该终点可能提供更完整的肿瘤缩小特征，纳入未来 ICI 临床试验的设计中。然而，需要进一步的研究来确认这种方法。
