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Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab.

Publication ,  Journal Article
Ince, WL; Jubb, AM; Holden, SN; Holmgren, EB; Tobin, P; Sridhar, M; Hurwitz, HI; Kabbinavar, F; Novotny, WF; Hillan, KJ; Koeppen, H
Published in: J Natl Cancer Inst
July 6, 2005

BACKGROUND: A recent phase III trial showed that the addition of bevacizumab, a monoclonal antibody to vascular endothelial growth factor-A, to first-line irinotecan, 5-fluorouracil, and leucovorin (IFL) prolonged median survival in patients with metastatic colorectal cancer. We carried out a retrospective analysis of patients in the trial to evaluate whether mutation status of k-ras, b-raf, or p53 or P53 expression could predict which patients were more likely to respond to bevacizumab. METHODS: Microdissected tumors from 295 patients (274 primary tumors, 21 metastases) were subject to DNA sequence analysis to identify mutations in k-ras, b-raf, and p53. Nuclear P53 expression was determined by immunohistochemistry. Hazard ratios and 95% confidence intervals (CI) for overall survival were estimated using Cox regression analysis. RESULTS: In all biomarker subgroups, estimated hazard ratios for risk of death were less than 1 for bevacizumab-treated patients as compared with those for placebo-treated patients. Mutations in k-ras and/or b-raf were observed in 88 of 213 patients (41%). Hazard ratios for death among patients with tumors with wild-type k-ras/b-raf status, as compared with those of patients with mutations in one or both genes, were 0.51 (95% CI = 0.28 to 0.95) among those treated with IFL plus bevacizumab and 0.66 (95% CI = 0.37 to 1.18) among those treated with IFL plus placebo. Mutations in p53 were found in 139 of 205 patients (68%), and P53 was overexpressed in 191 of 266 patients (72%); neither p53 mutation nor P53 overexpression was statistically significantly associated with survival. CONCLUSIONS: We did not find a statistically significant relationship between mutations of k-ras, b-raf, or p53 and the increase in median survival associated with the addition of bevacizumab to IFL in metastatic colorectal cancer.

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Published In

J Natl Cancer Inst

DOI

EISSN

1460-2105

Publication Date

July 6, 2005

Volume

97

Issue

13

Start / End Page

981 / 989

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Treatment Outcome
  • Retrospective Studies
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogene Proteins B-raf
  • Prognosis
  • Predictive Value of Tests
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged
 

Citation

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Ince, W. L., Jubb, A. M., Holden, S. N., Holmgren, E. B., Tobin, P., Sridhar, M., … Koeppen, H. (2005). Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab. J Natl Cancer Inst, 97(13), 981–989. https://doi.org/10.1093/jnci/dji174
Ince, William L., Adrian M. Jubb, Scott N. Holden, Eric B. Holmgren, Patti Tobin, Meera Sridhar, Herbert I. Hurwitz, et al. “Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab.J Natl Cancer Inst 97, no. 13 (July 6, 2005): 981–89. https://doi.org/10.1093/jnci/dji174.
Ince WL, Jubb AM, Holden SN, Holmgren EB, Tobin P, Sridhar M, et al. Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab. J Natl Cancer Inst. 2005 Jul 6;97(13):981–9.
Ince, William L., et al. “Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab.J Natl Cancer Inst, vol. 97, no. 13, July 2005, pp. 981–89. Pubmed, doi:10.1093/jnci/dji174.
Ince WL, Jubb AM, Holden SN, Holmgren EB, Tobin P, Sridhar M, Hurwitz HI, Kabbinavar F, Novotny WF, Hillan KJ, Koeppen H. Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab. J Natl Cancer Inst. 2005 Jul 6;97(13):981–989.
Journal cover image

Published In

J Natl Cancer Inst

DOI

EISSN

1460-2105

Publication Date

July 6, 2005

Volume

97

Issue

13

Start / End Page

981 / 989

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Treatment Outcome
  • Retrospective Studies
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogene Proteins B-raf
  • Prognosis
  • Predictive Value of Tests
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged