Immortal time bias in the association between toxicity and response for immune checkpoint inhibitors: a meta-analysis

被引：126

作者：

Dall'Olio, Filippo Gustavo ^{[1
]}

Rizzo, Alessandro ^{[1
]}

Mollica, Veronica ^{[1
]}

Massucci, Maria ^{[1
]}

Maggio, Ilaria ^{[1
]}

Massari, Francesco ^{[1
]}

机构：

[1] Univ Bologna, Oncol Med, Azienda Osped, Via Albertoni 15, Bologna, Italy

来源：

IMMUNOTHERAPY | 2021年 / 13卷 / 03期

关键词：

advanced cancer; bias; immortal time; immune checkpoint; immunotherapy; IrAE; landmark; response; survival; toxicity; ADVERSE EVENTS PREDICT; THERAPEUTIC-EFFICACY; ADVANCED MELANOMA; NIVOLUMAB; SAFETY; OUTCOMES; BENEFIT;

D O I：

10.2217/imt-2020-0179

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Only a minority of studies addressing the association between immune-related adverse events (IrAE) and outcome considered the immortal time bias, with conflicting results. PubMed, Embase, Web of Science and Scopus were searched through 2 January 2020. Studies reporting the impact of IrAE on outcome in patients treated with antiprogrammed death receptor 1 or PD-L1 were included. Twenty nine articles were included. IrAEs were associated with improved outcomes with high heterogeneity. With a landmark approach, the association between IrAE and outcome remains significant but the effect size was smaller (hazard ratio 0.61 vs 0.41 for overall survival; p = 0.015; hazard ratio 0.66 vs 0.47 for progression-free survival, p = 0.029; odds ratio 2.59 vs 6.77 for overall response rate; p < 0.001), no significant heterogeneity. Our analysis suggests a confounding effect of immortal time bias and a real effect of IrAE on outcome.

引用

页码：257 / 270

页数：14

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