Explanatory Role of Conversion Surgery as a Mediator of the Mortality Risk Difference Between Patients With Unresectable Metastatic Colorectal Cancer Treated With First-Line Anti-EGFR Agents Versus Bevacizumab

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer Pub Date : 2024-05-25 DOI:10.1016/j.clcc.2024.05.008

Chien-Chou Su , Yi-Chia Su , Chih-Chien Wu , Pei-Ting Lee

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引用次数: 0

Abstract

Introduction

Bevacizumab and antiepidermal growth factor receptor-blocking (anti-EGFR) agents plus chemotherapy are first-line therapies for metastatic colorectal cancer (mCRC). Conversion surgery may improve outcomes; however, the extent to which it explains the difference in mortality rates among treatments is unclear. Herein, we aimed to assess the effects of conversion surgery on survival outcomes of patients with unresectable mCRC treated with bevacizumab and anti-EGFR agents.

Materials and methods

This retrospective cohort study included patients with mCRC treated with bevacizumab and anti-EGFR agents as first-line therapy. We estimated the direct and indirect effects of treatments by comparing the mortality risk associated with targeted therapy type. Hazard ratios (HR) and the corresponding confidence intervals (CI) were estimated. Mediation analysis was used to estimate hazard ratio differences, and the proportion mediated.

Results

A total of 5,106 patients were included. The natural indirect effect of conversion surgery reduced mortality risk (HR: 0.95; 95% CI, 0.93-0.97), with a mediated proportion of 42% after propensity score adjustment. In subgroup analyses, KRAS wild-type (HR: 0.94; 95% CI: 0.91-0.97), left tumor sidedness (HR: 0.94; 95% CI, 0.91-0.96), and liver resection (HR: 0.95; 95% CI, 0.93-0.98) were associated with reduced risks of mortality. The controlled and total direct effects of targeted therapy were associated with reduced mortality risk in the anti-EGFR-treated group compared to those in the bevacizumab-treated group; however, this effect was not statistically significant.

Conclusion

Conversion surgery may account for the difference in survival outcomes between users of the anti-EGFR agents and bevacizumab.

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转化手术是一线抗EGFR药物治疗与贝伐单抗治疗无法切除的转移性结直肠癌患者死亡率风险差异的中介因素之一。

简介：贝伐单抗和抗表皮生长因子受体阻断剂（抗 EGFR）加化疗是治疗转移性结直肠癌（mCRC）的一线疗法。转换手术可能会改善治疗效果，但它在多大程度上解释了不同疗法之间的死亡率差异尚不清楚。在此，我们旨在评估转换手术对接受贝伐单抗和抗EGFR药物治疗的无法切除的mCRC患者生存结果的影响：这项回顾性队列研究纳入了接受贝伐单抗和抗EGFR药物一线治疗的mCRC患者。通过比较与靶向治疗类型相关的死亡风险，我们估算了治疗的直接和间接效果。我们估算了危险比（HR）和相应的置信区间（CI）。中介分析用于估算危险比差异和中介比例：共纳入 5106 名患者。转换手术的自然间接效应降低了死亡风险（HR：0.95；95% CI，0.93-0.97），倾向评分调整后的中介比例为 42%。在亚组分析中，KRAS野生型（HR：0.94；95% CI：0.91-0.97）、左侧肿瘤（HR：0.94；95% CI：0.91-0.96）和肝脏切除（HR：0.95；95% CI：0.93-0.98）与死亡风险降低相关。与贝伐珠单抗治疗组相比，抗EGFR治疗组的死亡率风险降低与靶向治疗的控制效果和总直接效果有关；但这种影响在统计学上并不显著：转换手术可能是抗表皮生长因子受体（anti-EGFR）药物和贝伐珠单抗使用者生存结果不同的原因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical colorectal cancer 医学-肿瘤学

CiteScore

5.50

自引率

2.90%

发文量

审稿时长

27 days

期刊介绍： Clinical Colorectal Cancer is a peer-reviewed, quarterly journal that publishes original articles describing various aspects of clinical and translational research of gastrointestinal cancers. Clinical Colorectal Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of colorectal, pancreatic, liver, and other gastrointestinal cancers. The main emphasis is on recent scientific developments in all areas related to gastrointestinal cancers. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.