January 16, 2009 (San Francisco, California) — Routine screening of patients with metastatic colorectal cancer for KRAS mutations before initiating treatment with epidermal growth-factor receptor (EGFR) inhibitors, such as cetuximab (Erbitux, ImClone), could result in a substantial cost savings. In addition, it would save patients from having to undergo ineffective therapy, according to a study presented here at the 2009 Gastrointestinal Cancers Symposium.
"Upfront KRAS testing to limit cetuximab therapy to patients with wild-type KRAS tumors can result in drug cost savings of $604 million, if the annual [American] population with metastatic colorectal cancer undergoes first-line therapy with a cetuximab-containing regimen," said study author Veena Shankaran, MD, from Northwestern University Feinberg School of Medicine, in Chicago, Illinois.
"KRAS testing is being embraced by the oncology community, and it is becoming more the standard of care," she added. As previously reported by Medscape Oncology, patients with colorectal cancer who carry KRAS mutations have been shown not to respond to treatment with EGRF inhibitors.
Data from studies indicate that the prevalence of KRAS mutations ranges from 35.6% to 42.3% in all patients with metastatic colorectal cancer, according to Dr. Shankaran, although an even higher percentage has been recorded.
"Although not yet reflected in pharmaceutical labeling, practice guidelines and clinical trials have incorporated KRAS testing as a standard procedure prior to cetuximab use," said Dr. Shankaran during a press briefing. "In addition to preventing significant toxicities and ineffective therapy, routine use of KRAS testing will result in significant cost savings for the healthcare system."
Economic Model Estimates Cost Savings
In this study, Dr. Shankaran and colleagues created an economic model to estimate the cost savings with KRAS-based cetuximab use in a theoretical population of patients. The model was derived from publicly available lab and drug-cost data and cancer-incidence data from the American Cancer Society. Clinical data were drawn from a recent study by Van Cutsem and colleagues (J Clin Oncol 2007; 25[18S]:4000), which investigated first-line cetuximab-containing therapy.
"We determined the net dollars saved from withholding cetuximab in KRAS-mutant patients after upfront KRAS testing for all patients," said Dr. Shankaran. "Our model did not include the additional costs associated with clinic appointments, infusion visits, and managing toxicity.'
The researchers used the following cost estimates:
Annual incidence of patients with metastatic cancer: 28,274
Percent of patients with KRAS mutations: 35.6%
Cost of KRAS testing at a commercial laboratory: $452/test
Average wholesale price of cetuximab (based on an average body-surface area of 1.73 mg/m2): loading dose of 400 mg/m2 = $3986/dose; weekly dose of 250 mg/m2 = $2491/dose
Mean number of cetuximab infusions: 24
They calculated that the cost of KRAS testing for all patients was $13 million, and the cost of treating the estimated 10,065 patients with KRAS mutations came to a total of $617 million.
If cetuximab therapy is limited to the remaining patients with wild-type KRAS, the savings would be $617 million, Dr. Shankaran pointed out. And, after subtracting the estimated cost of KRAS testing for patients with metastatic colorectal cancer, there would be a net savings of $604 million.
"Upfront KRAS testing results in cost savings when anti-EGFR antibodies are used in refractory disease," said Dr. Shankaran. "The development of other validated predictive molecular markers will save enormous amounts of money for our healthcare system, and will spare patients ineffective and toxic therapies. This is especially important given the rising costs of cancer care."
ASCO Issues Clinical Opinion
In response to the mounting evidence, the American Society of Clinical Oncology (ASCO) has issued its first clinical opinion, in favor of KRAS testing, said session moderator Jennifer R. Obel, MD, assistant professor of medicine at Northwestern University, in Chicago. "If patients have KRAS mutations, they should not receive anti-EGF agents."
"We found a high concordance between the primary tumor and metastatic site with KRAS mutation status," said Dr. Obel. "It does not change or appear to change over the course of the illness. In my practice, I like to test patients upfront, as it helps plan the course of therapy and I know [whether or not] an important drug will . . . be available."
2009 Gastrointestinal Cancers Symposium (GICS). Abstract 298. Presented January 17, 2009:
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Cite this: Roxanne Nelson. GICS 2009: Huge Cost Savings From KRAS Testing in Metastatic Colorectal Cancer - Medscape - Jan 16, 2009.