Association of cabozantinib residual concentration (Ctrough) and blood clearance (Cl/F) with toxicity (tox) and progressive disease (PD) in metastatic renal cell carcinoma (mRCC) patients (pts): Results from a monocentric pharmacokinetics (PK) study.

• DOI: 10.1200/jco.2021.39.6_suppl.292
• Publication Date: 2021-03-02T17:06:00Z
• Authors: Luigi Cerbone; David Combarel; Stéphanie Foulon; Arthur Geraud; Carolina Alves; Emeline Colomba; Lucia Carril; Lisa Derosa; Ronan Flippot; Olivier Mir; Bernard Escudier; Angelo Paci; Laurence Albiges
• Keywords: Cabozantinib

292 Background: Cabozantinib is a TKI with substantial efficacy in mRCC. It associated relevant tox leading frequent dose modifications (DM) or drug discontinuations (DD). While an exposure/safety relation has been demonstrated for this drug, exposure/efficacy still unknown. Cl/F measure of elimination from blood plasma and lower cabozantinib previously increased DM rate Methods: We performed monocentric PK (INDS MR 5612140520) study patients Blood draw assessment was at least 8 hours the last dose. Ctrough estimated following equation: Ctrough=Cmeas*0,5DI-24/t1/2. were compared without PD pts vs SD/PR pts. Relevant defined either as G3-4 G2 to DD. Differences CL assessed between groups Mann Withney U test. Results: From 01.10.19 31.08.20 66 included analysis. Twenty one 29 observed. higher experiencing than those who did not: 624,6 ng/ml (IQR 494-1030,2 ng/ml) 505,2 329,2-910,2), p0.012. Conversely not tox1,85 l/h 1,4-2,2 l/h) 2.27 1,7-3,2), p 0.024. In pts, pts: 419ng/ml 317,2 -549,1 554 416,9-795,6), 0.0105, while patients: 2,6 2,14-3,44 1.9 (1,930 l/h;IQR 1,35-2,53 l/h); p= 0.011. Time day cycle 1 significatively longer non-tox numerically which have lowest highest Cl/F. Conclusions: toxicity should be alongside test; may decrease conversely increase time on treatment. [Table: see text]