aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer.

Antineoplastic Combined Chemotherapy Protocols / pharmacology Bevacizumab / pharmacology Biomarkers / metabolism Colorectal Neoplasms / drug therapy Comparative Genomic Hybridization / methods Female Humans Irinotecan / pharmacology Male Middle Aged Neoplasm Metastasis Oxaliplatin / pharmacology Prognosis Survival Analysis

Bevacizumab Colorectal cancer Irinotecan Oxaliplatin aCGH analysis

Journal

The oncologist

ISSN: 1549-490X

Titre abrégé: Oncologist

Pays: England

ID NLM: 9607837

Informations de publication

Date de publication:
03 2019

Historique:

received: 27 02 2018

accepted: 05 09 2018

pubmed: 15 11 2018

medline: 4 6 2020

entrez: 15 11 2018

Statut: ppublish

Résumé

The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, Chromosome 8q24.1-q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1-p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.

Sections du résumé

BACKGROUND

MATERIALS AND METHODS

DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG).

RESULTS

Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm,

CONCLUSION

Chromosome 8q24.1-q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC.

IMPLICATIONS FOR PRACTICE

Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1-p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.

Identifiants

DOI: 10.1634/theoncologist.2018-0119 PMID: 30425180 PMC: PMC6519767

pubmed: 30425180

pii: theoncologist.2018-0119

doi: 10.1634/theoncologist.2018-0119

pmc: PMC6519767

doi:

Substances chimiques

Biomarkers 0

Oxaliplatin 04ZR38536J

Bevacizumab 2S9ZZM9Q9V

Irinotecan 7673326042

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

327-337

Informations de copyright

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