Uptake of KRAS Testing and Anti-EGFR Antibody Use for Colorectal Cancer in the VA.

Abstract

Advances in precision oncology, including <i>RAS</i> testing to predict response to epidermal growth factor receptor monoclonal antibodies (EGFR mAbs) in colorectal cancer (CRC), can extend patients' lives. We evaluated uptake and clinical use of <i>KRAS</i> molecular testing, guideline recommended since 2010, in the Veterans Affairs Healthcare System (VA). We conducted a retrospective cohort study of patients with stage IV CRC diagnosed in the VA 2006-2015. We gathered clinical, demographic, molecular, and treatment data from the VA Corporate Data Warehouse and 29 commercial laboratories. We performed multivariable analyses of associations between patient characteristics, <i>KRAS</i> testing, and EGFR mAb treatment. Among 5,943 patients diagnosed with stage IV CRC, only 1,053 (17.7%) had <i>KRAS</i> testing. Testing rates increased from 2.3% in 2006 to 28.4% in 2013. In multivariable regression, older patients (odds ratio, 0.17; 95% CI, 0.09 to 0.32 for ≥ age 85 <i>v</i> < 45 years) and those treated in the Northeast and South regions were less likely, and those treated at high-volume CRC centers were more likely to have <i>KRAS</i> testing (odds ratio, 2.32; 95% CI, 1.48 to 3.63). Rates of potentially guideline discordant care were high: 64.3% (321/499) of <i>KRAS</i> wild-type (WT) went untreated with EGFR mAb and 8.8% (401/4,570) with no <i>KRAS</i> testing received EGFR mAb. Among <i>KRAS</i>-WT patients, survival was better for patients who received EGFR mAb treatment (29.6 <i>v</i> 18.8 months; <i>P</i> < .001). We found underuse of <i>KRAS</i> testing in advanced CRC, especially among older patients and those treated at lower-volume CRC centers. We found high rates of potentially guideline discordant underuse of EGFR mAb in patients with <i>KRAS</i>-WT tumors. Efforts to understand barriers to precision oncology are needed to maximize patient benefit.