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KRAS Mutation in Stage III Colon Cancer and Clinical Outcome Following Intergroup Trial CALGB 89803

CLINICAL CANCER RESEARCH (2009)

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CLINICAL CANCER RESEARCH
卷 15, 期 23, 页码 7322-7329

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AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-09-1570

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Oncology

资金

  1. Baptist Cancer Institute CCOP, Memphis, TN - Lee S. Schwartzberg, M.D. [CA71323]
  2. Christiana Care Health Services, Inc. CCOP, Wilmington, DE - Stephen Grubbs, M.D. [CA45418]
  3. Dana-Farber Cancer Institute, Boston, MA - Eric P. Winer, M.D. [CA32291]
  4. Dartmouth Medical School - Norris Cotton Cancer Center, Lebanon, NH - Marc S. Ernstoff, M.D. [CA04326]
  5. Duke University Medical Center, Durham, NC - Jeffrey Crawford, M.D. [CA47577]
  6. Georgetown University Medical Center, Washington, DC Minetta C. Liu, M.D. [CA77597]
  7. Cancer Centers of the Carolinas, Greenville, SC - Jeffrey K. Giguere, M.D. [CA29165]
  8. Hematology-Oncology Associates of Central New York CCOP, Syracuse, NY - Jeffrey Kirshner, M.D. [CA45389]
  9. Long Island Jewish Medical Center, Lake Success, NY - Kanti R. Rai, M.D. [CA11028]
  10. Massachusetts General Hospital, Boston, MA - Jeffrey W. Clark, M.D. [CA12449]
  11. Memorial Sloan-Kettering Cancer Center, New York, NY Clifford A. Hudis, M.D. [CA77651]
  12. Missouri Baptist Medical Center, St. Louis, MO - Alan P. Lyss, M.D. [CA114558-02]
  13. Mount Sinai Medical Center, Miami, FL - Rogerio C. Lilenbaurn, M.D. [CA45564]
  14. Mount Sinai School of Medicine, New York, NY - Lewis R. Silverman, M.D. [CA04457]
  15. Nevada Cancer Research Foundation CCOP, Las Vegas, NV John A. Ellerton, M.D. [CA35421]
  16. North Shore-Long Island Jewish Health System, New Hyde Park, NY - Daniel Budman, M.D. [CA35279]
  17. Rhode Island Hospital, Providence, RI - William Sikov, M.D. [CA08025]
  18. Roswell Park Cancer Institute, Buffalo, NY - Ellis Levine, M.D. [CA02599]
  19. Southeast Cancer Control Consortium Inc. CCOP, Goldsboro [CA45808]
  20. State University of New York Upstate Medical University, Syracuse [CA21060]
  21. Ohio State University Medical Center, Columbus, OH [CA77658]
  22. University of California at San Diego, San Diego, CA [CA11789]
  23. University of California at San Francisco, San Francisco [CA60138]
  24. University of Chicago, Chicago, IL [CA41287]
  25. University of Illinois MBCCOP, Chicago, IL [CA74811]
  26. University of Iowa, Iowa City, IA [CA47642]
  27. University of Maryland Greenebaurn Cancer Center, Baltimore, MD [CA31983]
  28. University of Massachusetts Medical School, Worcester [CA37135]
  29. University of Minnesota, Minneapolis, MN [CA16450]
  30. University of Missouri/Ellis Fischel Cancer Center, Columbia, MO [CA12046]
  31. University of Nebraska Medical Center, Omaha, NE [CA77298]
  32. University of North Carolina [CA47559]
  33. University of Tennessee Memphis, Memphis, TN [CA47555]
  34. University of Vermont, Burlington, VT [CA77406]
  35. Wake Forest University School of Medicine, Winston-Salem, NC [CA03927]
  36. Walter Reed Army Medical Center, Washington, DC [CA26806]
  37. Washington University School of Medicine, St. Louis, MO [CA77440]
  38. Weill Medical College of Cornell University, New York [CA07968]

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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. (Clin Cancer Res 2009;15(23):7322-9)

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