Best of ASCO - 2014 Annual Meeting

 

Welcome

Attend this session at the
2019 ASCO Annual Meeting!


Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)

Type: Poster Session

Time: Saturday June 1, 8:00 AM to 11:00 AM

Location: Hall A

Accumulation of active metabolite M-2 predicts overall survival (OS) of chemorefractory metastatic colorectal cancer patients treated with regorafenib (REGO).

Sub-category:
Pharmacology

Category:
Developmental Therapeutics and Tumor Biology (Nonimmuno)

Meeting:
2019 ASCO Annual Meeting

Abstract No:
3121

Poster Board Number:
Poster Session (Board #113)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 3121)

Author(s): Benoit Rousseau, Arezki Khaled Boukerma, Julie Henriques, Romain Cohen, Olivier Lucidarme, Christophe Borg, Christophe Tournigand, Stefano Chong Hun Kim, Jean-Baptiste Bachet, Thibault Mazard, Christophe Louvet, Benoist Chibaudel, Luis A. Diaz, Dewi Vernerey, Thierry Andre, Anne Hulin; Oncology Department, Hopital Henri Mondor, APHP, Creteil, France; Pharmacology Unit, Henri Mondor Hospital, APHP, Creteil, France; Methodology and Quality of Life Unit, Department of Oncology University Hospital, Besançon, France; Saint-Antoine Hospital, Paris, France; Radiology Unit, Pitié Salpétrière Hospital, APHP, Paris, France; Department of Medical Oncology, Besancon University Hospital, Besancon, France; Hopitaux Universitaires Henri Mondor, AP-HP, Créteil, France; Centre Hospitalier-Universitaire de Besançon, Besançon, France; Hospital Pitié-Salpêtrière, Paris, France; IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, Montpellier, France; Institut Mutualiste Montsouris, Paris, France; GERCOR, Paris, France; Memorial Sloan Kettering Cancer Center, New York, NY; Methodology and Quality of Life Unit, INSERM UMR 1098, University Hospital of Besançon, Besançon, France; Pharmacoloy Department, Hôpital Henri Mondor, Aphp, Créteil, France

Abstract Disclosures

Abstract:

Background: TEXCAN, a prospective phase II GERCOR study of treatment with REGO in chemorefractory metastatic colorectal cancer (mCRC) patients (NCT02699073) included a prospective pharmacokinetic (PK) ancillary study aiming to investigate correlations between OS and concentrations (C) of REGO and its active metabolites M-2 and M-5. Methods: 55 patients were included, with the same inclusion/exclusion criteria as CORRECT (NCT01103323), and treated orally with 160 mg REGO daily for 3 weeks on and 1 week off. 34 patients had PK samples at C1D15 and 26 at C2D15 for Cmin. REGO, M-2 and M-5 Cmin were measured by LC-MS/MS. PK analyses studied the link between OS and PK parameters: Cmin of REGO, M-2 and M-5 at C1 and accumulation of pharmacological active metabolites between C1 and C2, assessed by the C2/C1 ratio of M-2 or M-5 Cmin concentrations. Results: REGO, M-2 and M-5 Cmin [median (Q1-Q3)] were respectively 1.99 (1.03-2.73), 1.44 (0.89-2.49) and 1.61 (0.79-2.37) mg/L at C1D15 and 1.90 (1.10-2.76), 1.29 (0.77-2.24) and 1.17 (0.45-2.42) mg/L at C2D15. C2/C1 M-2 ratio and M-5 ratio medians were 0.82 (0.50-1.78) and 0.75 (0.41-1.93), respectively. Univariate analyses showed a major OS benefit in patients with C2/C1 M-2 ratio ≥median vs < median (12.6 vs 4.0 months respectively, hazard ratio = 0.35, 95% confidence interval 0.14-0.86, p-value = 0.023) but not for C2/C1 M-5 ratio ≥median. Multivariate analyses, including the CORRECT REGOSCORE groups, showedan independent 66% reduction in death risk in the group of patients with C2/C1 M-2 ratio ≥median. The C2/C1 M-2 ratio correlated with C1 REGO+M-2+M-5 (Csum) (0.53, p-value = 0.006). Restricted Cubic spline analysis showed an increased OS benefit as the C2/C1 M-2 ratio rises and when C1 Csum ranged between 2.5 and 5.5 mg/L. PK parameters were not associated with toxicities. Conclusions: M-2 accumulation between C1 and C2 is independently associated with improved OS in mCRC patients treated by REGO. M-2 accumulates and OS is favorable when C1 REGO+M-2+M-5 sum ranged between 2.5 and 5.5 mg/L. These results may lead to develop individual REGO dosage modification strategies based on PK monitoring. Clinical trial information: NCT02699073

 
Other Abstracts in this Sub-Category:

 

1. A modeling and simulation study of less frequent dosing of nivolumab 480 mg.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3115 First Author: Cody J. Peer
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Pharmacology

 

2. Correlation between NDRG1 gene polymorphism and neuropathy (N) in metastatic breast cancer (MBC) patients (pts) enrolled in the PAINTER study (Polymorphism And INcidence of Toxicity in ERibulin treatment).

Meeting: 2019 ASCO Annual Meeting Abstract No: 3116 First Author: Nicla Maria La Verde
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Pharmacology

 

3. Concomitant intake of abiraterone and food to increase pharmacokinetic exposure: Real-life data from a therapeutic drug monitoring program.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3117 First Author: Stefanie L. Groenland
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Pharmacology

 

More...