Plasma Cetuximab Concentrations Correlate With Survival in Patients With Advanced KRAS Wild Type Colorectal Cancer

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2023-12-01 DOI:10.1016/j.clcc.2023.08.006

Di Maria Jiang , Shruti Parshad , Luna Zhan , Hao-Wen Sim , Lillian L. Siu , Geoffrey Liu , Jeremy D. Shapiro , Timothy J. Price , Derek J. Jonker , Christos S. Karapetis , Andrew H. Strickland , Wenjiang Zhang , Mark Jeffery , Dongsheng Tu , Siobhan Ng , Sabe Sabesan , Jenny Shannon , Amanda Townsend , Chris J. O'Callaghan , Eric X. Chen

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引用次数: 0

Abstract

Background

Cetuximab is a standard of care therapy for patients with RAS wild-type (WT) advanced colorectal cancer. Limited data suggest a wide variation in cetuximab plasma concentrations after standard dosing regimens. We correlated cetuximab plasma concentrations with survival and toxicity.

Methods

The CO. 20 study randomized patients with RAS WT advanced colorectal cancer in a 1:1 ratio to cetuximab 400 mg/m² intravenously followed by weekly maintenance of 250 mg/m², plus brivanib 800 mg orally daily or placebo. Blood samples obtained at week 5 precetuximab treatment were analyzed by ELISA. Patients were grouped into tertiles based on plasma cetuximab concentrations. Cetuximab concentration tertiles were correlated with survival outcomes and toxicity. Patient demographic and biochemical parameters were evaluated as co-variables.

Results

Week 5 plasma cetuximab concentrations were available for 591 patients (78.8%). The median overall survival (OS) was 11.4 months and 7.8 months for patients in the highest (T3) and lowest tertiles (T1) respectively. On multivariable analysis, plasma cetuximab concentration was associated with OS (HR 0.66, 95% confidence interval [CI]: 0.53-0.83, P < .001, T3 vs. T1), and a trend towards progression-free survival (HR 0.82, 95% CI: 0.66-1.02, P = .07, T3 vs. T1). There was no association between cetuximab concentration and skin toxicity or diarrhea.

Conclusion

The standard cetuximab dosing regimen may not be optimal for all patients. Further pharmacokinetic studies are needed to optimize cetuximab dosing given the potential improvement in OS.

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血浆西妥昔单抗浓度与晚期KRAS野生型结直肠癌患者的生存率相关

背景:西妥昔单抗是RAS野生型(WT)晚期结直肠癌患者的标准护理治疗。有限的数据表明，在标准给药方案后，西妥昔单抗血浆浓度变化很大。我们将西妥昔单抗血浆浓度与生存和毒性联系起来。方法:CO. 20研究将RAS WT晚期结直肠癌患者按1:1的比例随机分配给西妥昔单抗400mg /m2静脉注射，随后每周维持250mg /m2，加布里伐尼布800mg每日口服或安慰剂。采用酶联免疫吸附试验(ELISA)分析治疗第5周的血样。根据血浆西妥昔单抗浓度将患者分组。西妥昔单抗浓度与生存结果和毒性相关。患者人口学和生化参数作为协变量进行评估。结果:591例患者(78.8%)获得第5周血浆西妥昔单抗浓度。最高(T3)和最低(T1)患者的中位总生存期(OS)分别为11.4个月和7.8个月。在多变量分析中，血浆西妥昔单抗浓度与OS相关(HR 0.66, 95%可信区间[CI]: 0.53-0.83, P < 0.001, T3与T1)，并与无进展生存趋势相关(HR 0.82, 95% CI: 0.66-1.02, P = 0.07, T3与T1)。西妥昔单抗浓度与皮肤毒性或腹泻之间没有关联。结论:标准西妥昔单抗给药方案并非适用于所有患者。考虑到对OS的潜在改善，需要进一步的药代动力学研究来优化西妥昔单抗的剂量。

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

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567