Does KRAS Testing in Metastatic Colorectal Cancer Impact Overall Survival? A Comparative Effectiveness Study in a Population-Based Sample.

Feigelson HS1, Zeng C1, Pawloski PA2, Onitilo AA3, Richards CS4, Johnson MA4, Kauffman TL5, Webster J5, Nyirenda C1, Alexander GL6, Hwang C7, Cross D8, McCarty CA9, Davis RL10, Schwarzkopf D5, Williams AE11, Honda S11, Daida Y11, Kushi LH12, Delate T13, Goddard KA5; CERGEN Study Team.

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Abstract

PURPOSE:

Epidermal 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 METHODS:

We 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.

RESULTS:

The 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.

CONCLUSION:

Implementation 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.