Meeting
2014 ASCO Annual Meeting
Constitutive single nucleotide polymorphisms (SNP) assessment for predicting tolerability and efficacy of triplet hepatic artery infusion (HAI) and intravenous cetuximab (IV-CET) in patients (pts) with liver metastases from colorectal cancer (LM-CRC) (European trial OPTILIV, NCT00852228).
Authors
Francis Levi
Medical Oncology Department, INSERM U776, Paul Brousse Hospital, Villejuif, France
Francis Levi , Abdoulaye Karaboué , Raphaël Saffroy , Elodie Peyric , Michel Ducreux , Denis Michel Smith , Mohamed Hebbar , Pasquale F. Innominato , Simon Pernot , Carlos Carvalho , Rosine Guimbaud , C. N. J. Focan , Mohamed Bouchahda , Rene Adam , Marie-Christine Etienne-Grimaldi , Gerard A. Milano , Antoinette Lemoine
Organizations
Medical Oncology Department, INSERM U776, Paul Brousse Hospital, Villejuif, France, INSERM U776, Paul Brousse Hospital, Villejuif, France, Hôpital Paul Brousse Biochemistry Department, University Paris Sud, Villejuif, France, Centre for Cutaneous Research, Blizard Institute, Queen Mary University of London, London, England, Institut Gustave Roussy, Villejuif, France, Hopital Saint André, Bordeaux, France, Medical Oncology Unit - Hôpital Huriez, Lille, France, Inserm U776, Sevice de Chronothérapie, Département de Cancérologie, Hôpital Paul Brouse, Villejuif, France, Hôpital Européen Georges Pompidou, Paris, France, Medical Oncology Unit, Hospital Fernando Fonesca, Amadora, Portugal, University Hospital of Purpan, Toulouse, France, CHC Clinique Saint Joseph, Liège, Belgium, Hepatobiliary Center and INSERM U776, Paul Brousse Hospital, Villejuif, France, Laboratoire d'Oncopharmacologie, Centre Antoine Lacassagne, Nice, France, Centre Antoine Lacassagne, Nice, France, Hôpital Paul Brousse, Service de Biochimie et Biologie Moléculaire, Villejuif, France
Research Funding
Other
Background: The combination of IV-CET and HAI of irinotecan , oxaliplatin and 5-fluorouracil displayed high activity as 2-4thchemotherapy line for initially unresectable wt KRAS LM-CRC, yielding a macroscopic complete resection rate (R0+R1) of 29.7% and an overall survival of 25.7 months (Ducreux, ASCO 2013). The purpose is to identify the pts whose constitutive SNPs predict for best outcomes on this neoadjuvant protocol. Methods: 192 constitutive SNPs from 36 pharmacogenetically-relevant genes were analysed in pt blood cells using the ADME PGx panel with the MassArray platform (Sequenom, USA). Relations between polymorphic genes with minor SNPs and grade distribution for main toxicities per pt over 6 courses, best tumor response, and R0+R1, were explored using Mann Whitney or Fisher Exact test. Results: Gene polymorphisms were assessed in 52/64 registered pts with unresectable LM-CRC (16F; 36M), aged 33-76 years with good PS (0-1: 98%) receiving IV-CET + IFO-HAI as 2nd line for 21 pts (40%) and 3rd-4thline for 31 pts (60%). Main grade 3-4 toxicities were neutropenia (40%), abdominal pain (29%), fatigue (21%), and diarrhea (17%). Objective response was achieved in 20 pts (39%). Secondary R0-R1 LM resection was performed in 14/52 pts (27%). None of the minor SNPs in the 36 genes studied was a potential predictor of LM resection, nor displayed any significant relation with pt characteristics except for Cyp2C19 and sex (p<0.05). Best objective response was associated with minor SNPs in SLC22A2 (p=0.049) and UGT2B15 (p=0.011). Neutropenia, fatigue and diarrhea were associated with minor SNPs in Cyp2C19 (p<0.05). Neutropenia was further related to minor SNPs in Cyp1A2 (p = 0.017) and SLC22A1 (p=0.027), while diarrhea was predicted by minor SNPs in Cyp2D6A (p<0.05). Conclusions: This selected pharmacogenetics analysis revealed six genes involved in drug metabolism and transport whose minor SNPs predicted safety and efficacy outcomes and could warrant treatment adjustment for pts on neoadjuvant triplet HAI and IV-CET for LM-CRC. Clinical trial information: NCT00852228.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Details
Session Type
Poster Session
Session Title
Gastrointestinal (Colorectal) Cancer
Track
Gastrointestinal Cancer—Colorectal and Anal
Sub Track
Colorectal Cancer
Clinical Trial Registration Number
NCT00852228
Citation
J Clin Oncol 32:5s, 2014 (suppl; abstr 3593)
DOI
10.1200/jco.2014.32.15_suppl.3593
Abstract #
3593
Poster Bd #
56
Abstract Disclosures
Similar Abstracts
First Author: Abdoulaye Karaboué
Abstract
2017 ASCO Annual Meeting
Vitamin K epoxide reductase complex subunit 1 (VKORC1): A pharmacogenomic predictor of response and survival in patients (pts) on triplet hepatic artery infusion (HAI) and intravenous cetuximab (IV-Cet) for initially unresectable liver metastases from colorectal cancer (uLM-CRC) (EU trial OPTILIV).
First Author: Francis Levi
Abstract
2024 ASCO Gastrointestinal Cancers Symposium
Efficacy and safety of LY3537982, a potent and highly selective KRAS G12C inhibitor in KRAS G12C-mutant GI cancers: Results from a phase 1 study.
First Author: Antoine Hollebecque
Abstract
2017 ASCO Annual Meeting
Pharmacogenomic determinants of cetuximab and oxaliplatin pharmacokinetics during combined intravenous cetuximab (IV-Cet) and triplet hepatic artery chronomodulated infusion in patients (pts) with initially unresectable liver metastases from colorectal cancer (uLM-CRC) (EU OPTILIV trial).
First Author: Abdoulaye Karaboue