Bevacizumab-based chemotherapy adaptive to pharmacokinetic of bevacizumab in first-line treatment of patients with unresectable metastatic colorectal cancer: A double-blind, multicenter, randomized phase III trial study (PHARBEVACOL trial).

Fiche publication

Date publication

mars 2025

Journal

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BORG Christophe , Pr BOUCHE Olivier , Pr LEPAGE Côme

Tous les auteurs :
Lecomte T, Giraudeau B, Phelip JM, Tournigand C, Ducreux M, Tougeron D, Lepage C, Mineur L, Laplaige P, Desgrippes R, Artru P, Borg C, Jary M, Bouché O, Metges JP, Guimbaud R, Aparicio T, Foubert F, Hautefeuille V, Muller M, Bouhier-Leporrier K, Darrius R, Lobet S, Monmousseau F, Bejan-Angoulvant T, Paintaud G, Ternant D

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/40044552

Résumé

Bevacizumab shows inter-individual pharmacokinetic variability, with an exposure-response relationship in metastatic colorectal cancer (mCRC) patients. This study explores whether a double dose of bevacizumab, compared to a standard dose, increases efficacy in mCRC patients treated with bevacizumab-based chemotherapy as first-line therapy and who have a low initial trough concentration of bevacizumab. PHARBEVACOL is a multicenter, randomized, double-blind, two-parallel group trial. All patients will receive first-line bi-weekly 5 mg/kg bevacizumab-based chemotherapy and those with low initial bevacizumab concentrations (≤15.5 mg/L) will be randomized to either continue the standard dose (5 mg/kg every 14 days) or receive a double dose (10 mg/kg every 14 days). The primary objective is to evaluate the effect of doubling dose on progression-free survival (PFS). During a screening phase, the first serum trough concentration will be measured on day 14, before the second infusion of bevacizumab. We hypothesize a 40 % PFS in the control group at 9 months versus 60 % in the study group, corresponding to a hazard ratio of 0.56. With 80 % power, a 5 % two-sided type I error, and a minimum 12-month follow-up, 116 patients need to be included. Since only 50 % of screened patients will be eligible for randomization, approximately 244 patients will be screened. Recruitment is scheduled to begin in February 2025.