TY - JOUR
T1 - Plasma Cetuximab Concentrations Correlate With Survival in Patients With Advanced KRAS Wild Type Colorectal Cancer
AU - Jiang, Di Maria
AU - Parshad, Shruti
AU - Zhan, Luna
AU - Sim, Hao-Wen
AU - Siu, Lillian L
AU - Liu, Geoffrey
AU - Shapiro, Jeremy D
AU - Price, Timothy J
AU - Jonker, Derek J
AU - Karapetis, Christos S
AU - Strickland, Andrew H
AU - Zhang, Wenjiang
AU - Jeffery, Mark
AU - Tu, Dongsheng
AU - Ng, Siobhan
AU - Sabesan, Sabe
AU - Shannon, Jenny
AU - Townsend, Amanda
AU - O'Callaghan, Chris J
AU - Chen, Eric X
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Overall survival
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=85171779634&partnerID=8YFLogxK
U2 - 10.1016/j.clcc.2023.08.006
DO - 10.1016/j.clcc.2023.08.006
M3 - Article
C2 - 37704538
AN - SCOPUS:85171779634
SN - 1533-0028
VL - 22
SP - 457
EP - 463
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
IS - 4
ER -
