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

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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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.

Original languageEnglish
Pages (from-to)457-463
Number of pages7
JournalClinical Colorectal Cancer
Volume22
Issue number4
Early online date23 Aug 2023
DOIs
Publication statusPublished - Dec 2023
Externally publishedYes

Keywords

  • Overall survival
  • Toxicity

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