Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample.
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 AN...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4006772?pdf=render |
| _version_ | 1811206200980668416 |
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| author | Heather Spencer Feigelson Chan Zeng Pamala A Pawloski Adedayo A Onitilo C Sue Richards Monique A Johnson Tia L Kauffman Jennifer Webster Carsie Nyirenda Gwen L Alexander Clara Hwang Deanna Cross Catherine A McCarty Robert L Davis Denise Schwarzkopf Andrew E Williams Stacey Honda Yihe Daida Lawrence H Kushi Thomas Delate Katrina A B Goddard CERGEN Study Team |
| author_facet | Heather Spencer Feigelson Chan Zeng Pamala A Pawloski Adedayo A Onitilo C Sue Richards Monique A Johnson Tia L Kauffman Jennifer Webster Carsie Nyirenda Gwen L Alexander Clara Hwang Deanna Cross Catherine A McCarty Robert L Davis Denise Schwarzkopf Andrew E Williams Stacey Honda Yihe Daida Lawrence H Kushi Thomas Delate Katrina A B Goddard CERGEN Study Team |
| author_sort | Heather Spencer Feigelson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T03:43:46Z |
| format | Article |
| id | doaj.art-fbf6847bbc4948d69580744e994f6ce5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T03:43:46Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fbf6847bbc4948d69580744e994f6ce52022-12-22T03:49:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9497710.1371/journal.pone.0094977Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample.Heather Spencer FeigelsonChan ZengPamala A PawloskiAdedayo A OnitiloC Sue RichardsMonique A JohnsonTia L KauffmanJennifer WebsterCarsie NyirendaGwen L AlexanderClara HwangDeanna CrossCatherine A McCartyRobert L DavisDenise SchwarzkopfAndrew E WilliamsStacey HondaYihe DaidaLawrence H KushiThomas DelateKatrina A B GoddardCERGEN Study TeamPURPOSE: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.http://europepmc.org/articles/PMC4006772?pdf=render |
| spellingShingle | Heather Spencer Feigelson Chan Zeng Pamala A Pawloski Adedayo A Onitilo C Sue Richards Monique A Johnson Tia L Kauffman Jennifer Webster Carsie Nyirenda Gwen L Alexander Clara Hwang Deanna Cross Catherine A McCarty Robert L Davis Denise Schwarzkopf Andrew E Williams Stacey Honda Yihe Daida Lawrence H Kushi Thomas Delate Katrina A B Goddard CERGEN Study Team Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample. PLoS ONE |
| title | Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample. |
| title_full | Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample. |
| title_fullStr | Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample. |
| title_full_unstemmed | Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample. |
| title_short | Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample. |
| title_sort | does kras testing in metastatic colorectal cancer impact overall survival a comparative effectiveness study in a population based sample |
| url | http://europepmc.org/articles/PMC4006772?pdf=render |
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