一线晚期非小细胞肺癌客观反缓解率和基于生存的终点之间的相关性

Introduction 介绍

The study objective was to estimate the relationship between objective response and survival-based endpoints by drug class, in first-line advanced non-small cell lung cancer (aNSCLC).

该研究的目的是估计一线晚期非小细胞肺癌（aNSCLC）的客观缓解和基于生存的终点之间的关系，按药物类别划分。

  Materials and methods 材料与方法

A systematic literature review identified randomized controlled trials (RCTs) of first-line aNSCLC therapies reporting overall survival (OS), progression-free survival (PFS), and/or objective response rate (ORR). Trial-level and arm-level linear regression models were fit, accounting for inclusion of immunotherapy (IO)-based or chemotherapy-only RCT arms. Weighted least squares-based R2 were calculated along with 95% confidence interval (CIs). For the main trial-level analysis of OS vs. ORR, the surrogate threshold effect was estimated. Exploratory analyses involved further stratification by: IO monotherapy vs. chemotherapy, dual-IO therapy vs. chemotherapy, and IO+chemotherapy vs. chemotherapy.

一项系统的文献综述确定了一线进展期非小细胞肺癌疗法的随机对照试验（RCTs），报告了总生存期（OS）、无进展生存期（PFS）和/或客观反应率（ORR）。在考虑到纳入基于免疫疗法（IO）或纯化疗的RCT组的情况下，拟合了临床研究层面和队列层面的线性回归模型。计算了基于加权最小二乘法的R2以及95%的置信区间（CIs）。对于OS与ORR的主要临床研究层面分析，估计了替代阈值效应。探索性分析包括进一步分层：IO单药治疗与化疗，双IO治疗与化疗，以及IO+化疗与化疗。

Results 结果

From 17,040 records, 57 RCTs were included. In the main analysis, trial-level associations between OS and ORR were statistically significant in both the IO-based and chemotherapy-only strata, with R2 estimates of 0.54 (95% CI: 0.26-0.81) and 0.34 (0.05-0.63), respectively. OS gains associated with a given ORR benefit were statistically significantly larger within IO vs. chemotherapy comparisons compared to chemotherapy vs. chemotherapy comparisons (p <0.001). Exploratory analysis suggested a trend by IO type: for a given change in ORR, ‘pure’ IO (IO monotherapy and dual-IO) vs. chemotherapy RCTs tended to have a larger OS benefit than IO+chemotherapy vs. chemotherapy RCTs. For ORR vs. PFS, trial-level correlations were strong in the IO-based vs. chemotherapy (R2 = 0.84; 0.72-0.95), and chemotherapy vs. chemotherapy strata (R2 = 0.69; 0.49-0.88). For OS vs. PFS, correlations were moderate in both strata (R2 = 0.49; 0.20-0.78 and R2 = 0.49; 0.23-0.76).

在17,040条记录中，纳入了57项RCTs。在主要分析中，OS和ORR之间的临床研究层面的关联在基于IO和纯化疗的分层中都有统计学意义，R2估计值分别为0.54（95%CI：0.26-0.81）和0.34（0.05-0.63）。在IO与化疗的比较中，与给定的ORR效益相关的OS收益在统计学上明显大于化疗与化疗比较（P<0.001）。探索性分析表明，IO类型有一个趋势：对于给定的ORR变化，"纯 "IO（IO单药和双IO）与化疗RCTs相比，OS获益往往大于IO+化疗与化疗RCTs。对于ORR与PFS，在基于IO与化疗（R2=0.84；0.72-0.95），以及化疗与化疗分层（R2=0.69；0.49-0.88），临床研究层面的相关性很强。对于OS与PFS，两个阶层的相关性都是中等的（R2 = 0.49；0.20-0.78和R2 = 0.49；0.23-0.76）。

Conclusions 结论

The larger OS benefit per unit of ORR benefit in IO-based RCTs compared to chemotherapy-only RCTs provides an important addition to the established knowledge regarding the durability and depth of response in IO-based treatments.

与单纯化疗的RCT相比，基于IO的RCT中每单位ORR的OS获益更大，这为基于IO的治疗中反应的持久性和深度的既定知识提供了重要补充。

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