Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado, United States of America.
Heather Spencer
HS
Feigelson
Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado, United States of America.
Chan
C
Zeng
HealthPartners Institute for Education and Research, Bloomington, Minnesota, United States of America.
Pamala A
PA
Pawloski
Department of Hematology/Oncology, Marshfield Clinic Weston Center, Weston, Wisconsin, and Marshfield Clinic Research Foundation, Marshfield, Wisconsin, United States of America; Clinical Epidemiology Unit, School of Population Health, University of Queensland, Brisbane, Queensland, Australia.
Adedayo A
AA
Onitilo
Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon, United States of America.
C Sue
CS
Richards
Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon, United States of America.
Monique A
MA
Johnson
The Center for Health Research Kaiser Permanente Northwest, Portland, Oregon, United States of America.
Tia L
TL
Kauffman
The Center for Health Research Kaiser Permanente Northwest, Portland, Oregon, United States of America.
Jennifer
J
Webster
Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado, United States of America.
Carsie
C
Nyirenda
Henry Ford Health System, Department of Public Health Sciences, Detroit, Michigan, United States of America.
Gwen L
GL
Alexander
Henry Ford Health System, Department of Internal Medicine, Division of Hematology/Oncology, Detroit, Michigan, United States of America.
Clara
C
Hwang
Marshfield Clinic Research Foundation, Marshfield, Wisconsin, United States of America.
Deanna
D
Cross
Essentia Institute of Rural Health, Duluth, Minnesota, United States of America.
Catherine A
CA
McCarty
Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, Tennessee, United States of America.
Robert L
RL
Davis
The Center for Health Research Kaiser Permanente Northwest, Portland, Oregon, United States of America.
Denise
D
Schwarzkopf
Center for Health Research, Kaiser Permanente Hawai'i, Honolulu, Hawaii, United States of America.
Andrew E
AE
Williams
Center for Health Research, Kaiser Permanente Hawai'i, Honolulu, Hawaii, United States of America.
Stacey
S
Honda
Center for Health Research, Kaiser Permanente Hawai'i, Honolulu, Hawaii, United States of America.
Yihe
Y
Daida
Division of Research, Kaiser Permanente Northern California, Oakland, California, United States of America.
Lawrence H
LH
Kushi
Kaiser Permanente Colorado, Pharmacy Department, Denver, Colorado, United States of America.
Thomas
T
Delate
The Center for Health Research Kaiser Permanente Northwest, Portland, Oregon, United States of America.
Katrina A B
KA
Goddard
D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012307:Risk Factors; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins