Meeting
2021 Genitourinary Cancers Symposium
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.
Authors
Luigi Cerbone
Departement de Medicine Oncologique, Gustave Roussy, Villejuif, France
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
Organizations
Departement de Medicine Oncologique, Gustave Roussy, Villejuif, France, Institut Gustave Roussy, Villejuif, France, Gustave Roussy, Paris, France, Gustave Roussy Cancer Campus, Villejuif, France, Gustave Roussy Cancer Campus, Paris Saclay University, Villejuif, France, Hosp. 12 De Octubre, Madrid, Spain, U1015 INSERM, Gustave Roussy Cancer Campus, Paris Saclay University, Villejuif, France, Gustave Roussy cancer Campus, Villejuif, France, Gustave Roussy Cancer Institute, Villejuif, France, Gustave Roussy, Villejuif, France, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Research Funding
No funding received
None.
Background: Cabozantinib is a TKI with a substantial efficacy in mRCC. It is associated with a relevant tox leading frequent dose modifications (DM) or drug discontinuations (DD). While an exposure/safety relation has been demonstrated for this drug, an exposure/efficacy relation is still unknown. Cl/F is a measure of elimination of a drug from blood or plasma and lower Cl/F of cabozantinib has been previously associated with increased DM rate in mRCC. Methods: We performed a monocentric PK (INDS MR 5612140520) study in patients with mRCC. Blood draw for assessment of cabozantinib PK was performed at least 8 hours from the last drug dose. Ctrough was estimated with the following equation: Ctrough=Cmeas*0,5DI-24/t1/2. Ctrough and Cl/F were compared in patients with or without a relevant tox and in PD pts vs SD/PR pts. Relevant tox was defined either as G3-4 tox or G2 tox leading to DM or DD. Differences in Ctrough and CL were assessed between the groups with Mann Withney U test. Results: From 01.10.19 to 31.08.20 66 pts were included in this analysis. Twenty one relevant tox and 29 PD were observed. Ctrough was higher in pts experiencing relevant tox than in those who did not: 624,6 ng/ml (IQR 494-1030,2 ng/ml) vs 505,2 ng/ml (IQR 329,2-910,2), p0.012. Conversely Cl/F was lower in relevant tox vs not tox1,85 l/h (IQR 1,4-2,2 l/h) vs 2.27 l/h (IQR 1,7-3,2), p 0.024. In PD pts, Ctrough was lower than in SD/PR pts: 419ng/ml (IQR 317,2 -549,1 ng/ml) vs 554 ng/ml (IQR 416,9-795,6), p 0.0105, while Cl/F was higher in PD patients: 2,6 l/h (IQR 2,14-3,44 l/h) vs SD/PR patients 1.9 l/h (1,930 l/h;IQR 1,35-2,53 l/h); p= 0.011. Time from day cycle 1 to PK blood draw was significatively longer in non-tox pts and numerically longer in PD pts, which have the lowest Ctrough and the highest Cl/F. Conclusions: Cabozantinib toxicity is associated to a higher Ctrough and a lower Cl/F. Cabozantinib PD is associated to a lower Ctrough and a higher Cl/F. Cl/F should be assessed alongside with Ctrough in Cabozantinib PK blood test; Ctrough may decrease and conversely Cl/F may increase with time on treatment.
| Variable | Tox (21) | Non Tox(45) | p | PD(29) | SD/PR(37) | p |
|---|---|---|---|---|---|---|
| Age median (IQR) | 58 (52.5-66) | 61 (55-69) | .37 | 58 (52-65) | 61.5 (54.3-69) | .53 |
| Histology (ccRCC) | 16/21 | 36/45 | .72 | 22/29 | 29/37 | .26 |
| Does intensity median (IQR) | 40 (40-60) | 42.8 (40-60) | .5 | 40 (40-60) | 40 (28.8-55.7) | .15 |
| Time from C1D1 to blood draw, weeks, median (IQR) | 13 (4.3-45.7) | 44 (12.2-95.3) | .03 | 39.4 (24.9-66.3) | 17.8 (7.6-91) | .1 |
IQR: Interquartile range Italics: p significative.
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Abstract Details
Session Type
Poster Session
Session Title
Poster Session: Renal Cell Cancer
Track
Renal Cell Cancer
Sub Track
Patient-Reported Outcomes and Real-World Evidence
Citation
J Clin Oncol 39, 2021 (suppl 6; abstr 292)
DOI
10.1200/JCO.2021.39.6_suppl.292
Abstract #
292
Poster Bd #
Online Only
Abstract Disclosures
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