KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803

Shuji Ogino*, Jeffrey A. Meyerhardt, Natsumi Irahara, Donna Niedzwiecki, Donna Hollis, Leonard B. Saltz, Robert J. Mayer, Paul Schaefer, Renaud Whittom, Alexander Hantel, Al B Benson III, Richard M. Goldberg, Monica M. Bertagnolli, Charles S. Fuchs

*Corresponding author for this work

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Purpose: Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy (cetuximab or panitumumab). It remains uncertain, however, whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy. Methods: We conducted a study of 508 cases identified among 1,264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) in 1999-2001 (CALGB 89803). KRAS mutations were detected in 178 tumors (35%) by pyrosequencing. Kaplan-Meier and Cox proportional hazard models assessed the prognostic significance of KRAS mutation and adjusted for potential confounders including age, sex, tumor location, tumor/ node stage, performance status, adjuvant chemotherapy arm, and microsatellite instability status. Results: Compared with patients with KRAS-wild-type tumors, patients with KRAS-mutated tumors did not experience any difference in disease-free, recurrence-free, or overall survival. The 5-year disease-free, recurrence-free, and overall survival rates (KRAS-mutated versus KRAS-wild-type patients) were 62% versus 63% (log-rank P = 0.89), 64% versus 66% (P = 0.84), and 75% versus 73% (P = 0.56), respectively. The effect of KRAS mutation on patient survival did not significantly differ according to clinical features, chemotherapy arm, or microsatellite instability status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. Conclusions: In this large trial of chemotherapy in stage III colon cancer patients, KRAS mutational status was not associated with any significant influence on disease-free or overall survival.

Original languageEnglish (US)
Pages (from-to)7322-7329
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number23
DOIs
StatePublished - Dec 1 2009

Fingerprint

Colonic Neoplasms
Mutation
Adjuvant Chemotherapy
Microsatellite Instability
irinotecan
Neoplasms
Epidermal Growth Factor Receptor
Epigenomics
Survival
Recurrence
Drug Therapy
Leucovorin
Proportional Hazards Models
Fluorouracil
Colorectal Neoplasms
Carcinogenesis
Survival Rate
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ogino, S., Meyerhardt, J. A., Irahara, N., Niedzwiecki, D., Hollis, D., Saltz, L. B., ... Fuchs, C. S. (2009). KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803. Clinical Cancer Research, 15(23), 7322-7329. https://doi.org/10.1158/1078-0432.CCR-09-1570
Ogino, Shuji ; Meyerhardt, Jeffrey A. ; Irahara, Natsumi ; Niedzwiecki, Donna ; Hollis, Donna ; Saltz, Leonard B. ; Mayer, Robert J. ; Schaefer, Paul ; Whittom, Renaud ; Hantel, Alexander ; Benson III, Al B ; Goldberg, Richard M. ; Bertagnolli, Monica M. ; Fuchs, Charles S. / KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 23. pp. 7322-7329.
@article{9999665f6ad243bab6e443539fb1bae4,
title = "KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803",
abstract = "Purpose: Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy (cetuximab or panitumumab). It remains uncertain, however, whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy. Methods: We conducted a study of 508 cases identified among 1,264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) in 1999-2001 (CALGB 89803). KRAS mutations were detected in 178 tumors (35{\%}) by pyrosequencing. Kaplan-Meier and Cox proportional hazard models assessed the prognostic significance of KRAS mutation and adjusted for potential confounders including age, sex, tumor location, tumor/ node stage, performance status, adjuvant chemotherapy arm, and microsatellite instability status. Results: Compared with patients with KRAS-wild-type tumors, patients with KRAS-mutated tumors did not experience any difference in disease-free, recurrence-free, or overall survival. The 5-year disease-free, recurrence-free, and overall survival rates (KRAS-mutated versus KRAS-wild-type patients) were 62{\%} versus 63{\%} (log-rank P = 0.89), 64{\%} versus 66{\%} (P = 0.84), and 75{\%} versus 73{\%} (P = 0.56), respectively. The effect of KRAS mutation on patient survival did not significantly differ according to clinical features, chemotherapy arm, or microsatellite instability status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. Conclusions: In this large trial of chemotherapy in stage III colon cancer patients, KRAS mutational status was not associated with any significant influence on disease-free or overall survival.",
author = "Shuji Ogino and Meyerhardt, {Jeffrey A.} and Natsumi Irahara and Donna Niedzwiecki and Donna Hollis and Saltz, {Leonard B.} and Mayer, {Robert J.} and Paul Schaefer and Renaud Whittom and Alexander Hantel and {Benson III}, {Al B} and Goldberg, {Richard M.} and Bertagnolli, {Monica M.} and Fuchs, {Charles S.}",
year = "2009",
month = "12",
day = "1",
doi = "10.1158/1078-0432.CCR-09-1570",
language = "English (US)",
volume = "15",
pages = "7322--7329",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "23",

}

Ogino, S, Meyerhardt, JA, Irahara, N, Niedzwiecki, D, Hollis, D, Saltz, LB, Mayer, RJ, Schaefer, P, Whittom, R, Hantel, A, Benson III, AB, Goldberg, RM, Bertagnolli, MM & Fuchs, CS 2009, 'KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803', Clinical Cancer Research, vol. 15, no. 23, pp. 7322-7329. https://doi.org/10.1158/1078-0432.CCR-09-1570

KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803. / Ogino, Shuji; Meyerhardt, Jeffrey A.; Irahara, Natsumi; Niedzwiecki, Donna; Hollis, Donna; Saltz, Leonard B.; Mayer, Robert J.; Schaefer, Paul; Whittom, Renaud; Hantel, Alexander; Benson III, Al B; Goldberg, Richard M.; Bertagnolli, Monica M.; Fuchs, Charles S.

In: Clinical Cancer Research, Vol. 15, No. 23, 01.12.2009, p. 7322-7329.

Research output: Contribution to journalArticle

TY - JOUR

T1 - KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803

AU - Ogino, Shuji

AU - Meyerhardt, Jeffrey A.

AU - Irahara, Natsumi

AU - Niedzwiecki, Donna

AU - Hollis, Donna

AU - Saltz, Leonard B.

AU - Mayer, Robert J.

AU - Schaefer, Paul

AU - Whittom, Renaud

AU - Hantel, Alexander

AU - Benson III, Al B

AU - Goldberg, Richard M.

AU - Bertagnolli, Monica M.

AU - Fuchs, Charles S.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - Purpose: Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy (cetuximab or panitumumab). It remains uncertain, however, whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy. Methods: We conducted a study of 508 cases identified among 1,264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) in 1999-2001 (CALGB 89803). KRAS mutations were detected in 178 tumors (35%) by pyrosequencing. Kaplan-Meier and Cox proportional hazard models assessed the prognostic significance of KRAS mutation and adjusted for potential confounders including age, sex, tumor location, tumor/ node stage, performance status, adjuvant chemotherapy arm, and microsatellite instability status. Results: Compared with patients with KRAS-wild-type tumors, patients with KRAS-mutated tumors did not experience any difference in disease-free, recurrence-free, or overall survival. The 5-year disease-free, recurrence-free, and overall survival rates (KRAS-mutated versus KRAS-wild-type patients) were 62% versus 63% (log-rank P = 0.89), 64% versus 66% (P = 0.84), and 75% versus 73% (P = 0.56), respectively. The effect of KRAS mutation on patient survival did not significantly differ according to clinical features, chemotherapy arm, or microsatellite instability status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. Conclusions: In this large trial of chemotherapy in stage III colon cancer patients, KRAS mutational status was not associated with any significant influence on disease-free or overall survival.

AB - Purpose: Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy (cetuximab or panitumumab). It remains uncertain, however, whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy. Methods: We conducted a study of 508 cases identified among 1,264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) in 1999-2001 (CALGB 89803). KRAS mutations were detected in 178 tumors (35%) by pyrosequencing. Kaplan-Meier and Cox proportional hazard models assessed the prognostic significance of KRAS mutation and adjusted for potential confounders including age, sex, tumor location, tumor/ node stage, performance status, adjuvant chemotherapy arm, and microsatellite instability status. Results: Compared with patients with KRAS-wild-type tumors, patients with KRAS-mutated tumors did not experience any difference in disease-free, recurrence-free, or overall survival. The 5-year disease-free, recurrence-free, and overall survival rates (KRAS-mutated versus KRAS-wild-type patients) were 62% versus 63% (log-rank P = 0.89), 64% versus 66% (P = 0.84), and 75% versus 73% (P = 0.56), respectively. The effect of KRAS mutation on patient survival did not significantly differ according to clinical features, chemotherapy arm, or microsatellite instability status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. Conclusions: In this large trial of chemotherapy in stage III colon cancer patients, KRAS mutational status was not associated with any significant influence on disease-free or overall survival.

UR - http://www.scopus.com/inward/record.url?scp=73149107502&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73149107502&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-09-1570

DO - 10.1158/1078-0432.CCR-09-1570

M3 - Article

C2 - 19934290

AN - SCOPUS:73149107502

VL - 15

SP - 7322

EP - 7329

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 23

ER -