Abstract
PurposeEpidermal growth factor receptor (EGFR) inhibitors are approved for treating metastatic colorectal cancer (CRC); KRAS mutation testing is recommended prior to treatment. We conducted a non-inferiority analysis to examine whether KRAS testing has impacted survival in CRC patients.Patients and MethodsWe included 1186 metastatic CRC cases from seven health plans. A cutpoint of July, 2008, was used to define two KRAS testing time period groups: “pre-testing” (n = 760 cases) and “post-testing” (n = 426 cases). Overall survival (OS) was estimated, and the difference in median OS between the groups was calculated. The lower bound of the one-sided 95% confidence interval (CI) for the difference in survival was used to test the null hypothesis of post-testing inferiority. Multivariable Cox regression models were constructed to adjust for covariates.ResultsThe median unadjusted OS was 15.4 months (95% CI: 14.0–17.5) and 12.8 months (95% CI: 10.0–15.2) in the pre- and post-testing groups, respectively. The OS difference was −2.6 months with one-sided 95% lower confidence bound of −5.13 months, which was less than the non-inferiority margin (−5.0 months, unadjusted p = 0.06), leading to a failure to reject inferiority of OS in the post-testing period. In contrast, in the adjusted analysis, OS non-inferiority was identified in the post-testing period (p = 0.001). Sensitivity analyses using cutpoints before and after July, 2008, also met the criteria for non-inferiority.ConclusionImplementation of KRAS testing did not influence CRC OS. Our data support the use of KRAS testing to guide administration of EGFR inhibitors for treatment of metastatic CRC without diminished OS.
Highlights
While survival rates in individuals with colorectal cancer (CRC) have increased significantly in recent years, survival among patients with metastatic CRC remains poor, with five-year survival of just 12% [1]
The Overall survival (OS) difference was 22.6 months with one-sided 95% lower confidence bound of 25.13 months, which was less than the non-inferiority margin (25.0 months, unadjusted p = 0.06), leading to a failure to reject inferiority of OS in the post-testing period
Our data support the use of KRAS testing to guide administration of epidermal growth factor receptor (EGFR) inhibitors for treatment of metastatic CRC without diminished OS
Summary
While survival rates in individuals with colorectal cancer (CRC) have increased significantly in recent years, survival among patients with metastatic CRC remains poor, with five-year survival of just 12% [1]. In April 2009, the American Society of Clinical Oncology (ASCO) recommended that patients with metastatic CRC who are candidates for EGFR inhibitors have their tumor tested for KRAS mutations, and that those with a KRAS mutation in codon 12 or 13 not receive anti-EGFR treatment [3]. The FDA recommended relabeling of EGFR inhibitors to refer to KRAS testing [5]. The impact of this is not insignificant, as up to 40% of CRC tumors harbor a KRAS mutation [6,7,8]. For patients with these mutations, an alternative targeted therapy does not currently exist
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