非小细胞肺癌免疫治疗随机试验中性别无进展生存替代的异质性。

IF 4.1 Q2 ONCOLOGY
Eleonora Pagan, Isabella Sala, Laura Pala, Fabrizio Natali, Federico Merlo, Chiara Oriecuia, Claudia Specchia, Tommaso De Pas, Chiara Catania, Emilia Cocorocchio, Daniele Laszlo, Giovanni Ceresoli, Marzia Locatelli, Priscilla Cascetta, Flaminia Facella, Benedetta Tinterri, Martina Pino, Jacopo Canzian, Giuseppe Giaccone, Vincenzo Bagnardi, Fabio Conforti
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引用次数: 0

摘要

背景:在测试晚期非小细胞肺癌(NSCLC)患者免疫检查点抑制剂(ICIs)的随机临床试验(rct)中,试验水平的无进展生存期(PFS)替代总生存期(OS)受到几个临床病理因素的影响。然而,根据患者的性别,PFS代孕的潜在异质性从未被调查过。方法:纳入根据患者性别报告PFS和OS风险比(HR)的晚期NSCLC患者的ICIs单药或联合化疗的随机对照试验。主要目的是评估PFS(替代终点)和OS(参考终点)之间试验水平相关性的基于性别的异质性,总体和按治疗类型定义的亚组(ICIs为单药治疗vs ICIs加化疗)。我们使用决定系数(R2)来量化代孕。结果:共纳入20项随机对照试验,共计7528例男性患者和3008例女性患者。总体而言,OS-HR和PFS-HR之间的关联是中等的:实验组中治疗类型调整后的模型R2为0.69 (95% CI, 0.34至0.88)。性别分类分析显示PFS代孕的异质性:男性的相关性较强(校正R2=0.77; 95% CI, 0.56 ~ 0.89),但女性的相关性较弱(校正R2=0.31; 95% CI, 0.03 ~ 0.63)。在治疗类型亚组分析和交叉验证分析中获得一致的结果。结论:在晚期NSCLC患者单独使用ICIs或联合化疗的随机对照试验中,PFS是男性OS的可靠替代终点,而不是女性OS。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Heterogeneity of progression-free survival surrogacy by sex in randomized trials testing immunotherapy in non-small cell lung cancer.

Heterogeneity of progression-free survival surrogacy by sex in randomized trials testing immunotherapy in non-small cell lung cancer.

Heterogeneity of progression-free survival surrogacy by sex in randomized trials testing immunotherapy in non-small cell lung cancer.

Background: The surrogacy of progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancers (NSCLC) is influenced by several clinical-pathological factors. However, potential heterogeneity of PFS surrogacy according to patients' sex has never been investigated.

Methods: RCTs testing ICIs as monotherapy or combined with chemotherapy in patients with advanced NSCLC reporting hazard ratios (HRs) for PFS and OS according to patients' sex were included. The main objective was to assess sex-based heterogeneity in the trial-level association between PFS (surrogate endpoint) and OS (reference endpoint), overall and in subgroups defined by treatment type (ICIs as monotherapy vs ICIs plus chemotherapy). We used the coefficient of determination (R2) to quantify surrogacy.

Results: Twenty RCTs, for a total of 7528 male and 3008 female patients, were included. Overall, the association between OS-HR and PFS-HR was moderate: the R2 from a model adjusted by the type of treatment administered in the experimental arm was 0.69 (95% confidence interval [CI] = 0.34 to 0.88). Sex-disaggregated analysis showed heterogeneity in PFS surrogacy: the association was strong in male patients (adjusted R2 = 0.77; 95% CI = 0.56 to 0.89), but poor in female (adjusted R2 = 0.31, 95% CI = 0.03 to 0.63). Consistent results were obtained in subgroups analyses by treatment type, and in cross-validation analysis.

Conclusions: In RCTs testing ICIs alone or combined with chemotherapy in patients with advanced NSCLC, PFS is a robust surrogate endpoint for OS in male patients but not in female.

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来源期刊
JNCI Cancer Spectrum
JNCI Cancer Spectrum Medicine-Oncology
CiteScore
7.70
自引率
0.00%
发文量
80
审稿时长
18 weeks
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