[Observational study on conditions for access to the analysis of KRAS mutation in patients with metastatic colorectal cancer receiving panitumumab treatment]

Bull Cancer. 2012 Jul-Aug;99(7-8):743-51. doi: 10.1684/bdc.2012.1612.
[Article in French]

Abstract

KRAS status is now a mandatory prerequisite in order to treat metastatic colorectal patients with anti-Epidermal Growth Factor Receptor (EGFR) antibodies, such as cetuximab or panitumumab. KRAS mutations are unambiguously linked to a lack of response to these targeted therapies. Because of the major clinical impact of KRAS status, an observational study has been designed in France, focusing on the ability to perform KRAS testing between october 2008 and october 2009. The study was retro-prospective, national, multicentric, descriptive and non interventional, concerning public and private institutions and KRAS non mutated patients treated with panitumumab. The primary objective of this study was to evaluate delays between the genotyping KRAS request and the result. Secondary objectives were: type of genotyping requests (systematic/prospective or specific/retrospective), prevalence of the different genotyping techniques, delays between the genotyping KRAS request and therapy with panitumumab. Overall, 329 patients from 66 centres have been included. About half of them belonged to private institutions. The results were obtained with a mean delay of 33.4 ± 39.8 days (CI 95%: [28.8; 37.9] days; median: 24 days). Most of KRAS genotyping tests were performed on specific requests (65.3%), from a primary tumor (80.4%) and from a surgical specimen (73.9%). The more frequently used techniques for KRAS genotyping were: real time PCR (36.2%), sequencing (24.8%) and pyrosequencing (13.2%). This study emphasizes the functionality of cancer molecular genetic platforms dedicated to KRAS genotyping, which allow the use of molecular predictive biomarkers by different medical institutions. This study also underlines the broad spectrum of genotyping techniques (no consensus). The delays of response are still longer than expected but might be improved by optimizing the procedures.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis / methods
  • DNA Mutational Analysis / standards
  • ErbB Receptors / immunology
  • Female
  • Fluorouracil / administration & dosage
  • France
  • Genes, ras / genetics*
  • Genetic Testing / methods
  • Genetic Testing / standards*
  • Genotype
  • Humans
  • Irinotecan
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Panitumumab
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction / standards
  • Retrospective Studies
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Panitumumab
  • Irinotecan
  • ErbB Receptors
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol
  • IFL protocol