KRAS testing and epidermal growth factor receptor inhibitor treatment for colorectal cancer in community settings

Cancer Epidemiol Biomarkers Prev. 2013 Jan;22(1):91-101. doi: 10.1158/1055-9965.EPI-12-0545. Epub 2012 Nov 15.

Abstract

Background: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of KRAS testing.

Methods: We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven integrated health care delivery systems with a combined membership of 5.5 million. We used electronic medical records and targeted manual chart review to capture the complexity and breadth of real-world clinical oncology care.

Results: Overall, 428 patients (36%) received KRAS testing during their clinical care, and 266 (22%) were treated with EGFR inhibitors. Age at diagnosis (P = 0.0034), comorbid conditions (P = 0.0316), and survival time from diagnosis (P < 0.0001) influence KRAS testing and EGFR inhibitor prescribing. The proportion who received KRAS testing increased from 7% to 97% for those treated in 2006 and 2010, respectively, and 83% of all treated patients had a KRAS wild-type genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing decreased from 26 months (2006) to 10 months (2009).

Conclusions: These findings show rapid uptake and incorporation of this predictive biomarker into clinical oncology care.

Impact: In this delivery setting, KRAS testing is widely used to guide treatment decisions with EGFR inhibitors in patients with mCRCs. An important future research goal is to evaluate utilization of KRAS testing in other delivery settings in the United States.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antineoplastic Agents / administration & dosage
  • Cohort Studies
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Confidence Intervals
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • ErbB Receptors / administration & dosage
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • Genetic Testing
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Molecular Targeted Therapy*
  • Multivariate Analysis
  • Mutation
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Residence Characteristics
  • Retrospective Studies
  • Risk Assessment
  • Survival Rate
  • Treatment Outcome
  • United States
  • ras Proteins / genetics*

Substances

  • Antineoplastic Agents
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins