KRAS and colorectal cancer: Ethical and pragmatic issues in effecting real-time change in oncology clinical trials and practice

Charles D. Blanke, Richard M. Goldberg, Axel F Grothey, Margaret Mooney, Nancy Roach, Leonard B. Saltz, J. WELCH John, A. WOOD William, Neal J. Meropol

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Systemic therapy has led to a median survival time for patients with advanced colorectal cancer (CRC) almost fourfold longer than that expected with best supportive care, an outcome achieved through combining chemotherapeutic and targeted biologic agents. Although the latter can include anti-epidermal growth factor receptor antibodies, such as cetuximab and panitumumab, we now have strong evidence that patients whose tumors harbor mutated KRAS will not benefit from this class of agent. Acceptance of the reliability and importance of the KRAS data took several years to evolve, however, for a variety of reasons. The timeline from the presentation and publication of small, retrospective phase II studies to widespread acceptance of the KRAS predictive value and changes in behavior-specifically, modifications of ongoing national trials in advanced/ metastatic CRC, changes in national guidelines and practice patterns, and adjustments to the labeled indications for the monoclonal antibodies-was lengthy. In this commentary, we discuss whether or not the process of data disclosure regarding KRAS status and treatment of advanced CRC patients was effective in permitting timely decisions regarding ongoing publicly funded clinical trials and whether or not such de- cisions were rational and ethical. The overall goals are to highlight lessons learned regarding early disclosure of clinical trial results, as well as vetting and adoption of new scientific data, and to propose modifications for handling similar situations in the future.

Original languageEnglish (US)
Pages (from-to)1061-1068
Number of pages8
JournalOncologist
Volume16
Issue number8
DOIs
StatePublished - Aug 2011

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Ethics
Colorectal Neoplasms
Disclosure
Clinical Trials
Social Adjustment
Behavior Therapy
Biological Factors
Practice Guidelines
Epidermal Growth Factor Receptor
Publications
Monoclonal Antibodies
Survival
Antibodies
Therapeutics
Neoplasms
TimeLine
Cetuximab
panitumumab

Keywords

  • Clinical trials
  • Colorectal neoplasms
  • Ethics
  • KRAS

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Blanke, C. D., Goldberg, R. M., Grothey, A. F., Mooney, M., Roach, N., Saltz, L. B., ... Meropol, N. J. (2011). KRAS and colorectal cancer: Ethical and pragmatic issues in effecting real-time change in oncology clinical trials and practice. Oncologist, 16(8), 1061-1068. https://doi.org/10.1634/theoncologist.2011-0011

KRAS and colorectal cancer : Ethical and pragmatic issues in effecting real-time change in oncology clinical trials and practice. / Blanke, Charles D.; Goldberg, Richard M.; Grothey, Axel F; Mooney, Margaret; Roach, Nancy; Saltz, Leonard B.; John, J. WELCH; William, A. WOOD; Meropol, Neal J.

In: Oncologist, Vol. 16, No. 8, 08.2011, p. 1061-1068.

Research output: Contribution to journalArticle

Blanke, CD, Goldberg, RM, Grothey, AF, Mooney, M, Roach, N, Saltz, LB, John, JWELCH, William, AWOOD & Meropol, NJ 2011, 'KRAS and colorectal cancer: Ethical and pragmatic issues in effecting real-time change in oncology clinical trials and practice', Oncologist, vol. 16, no. 8, pp. 1061-1068. https://doi.org/10.1634/theoncologist.2011-0011
Blanke, Charles D. ; Goldberg, Richard M. ; Grothey, Axel F ; Mooney, Margaret ; Roach, Nancy ; Saltz, Leonard B. ; John, J. WELCH ; William, A. WOOD ; Meropol, Neal J. / KRAS and colorectal cancer : Ethical and pragmatic issues in effecting real-time change in oncology clinical trials and practice. In: Oncologist. 2011 ; Vol. 16, No. 8. pp. 1061-1068.
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