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


Authors: Blanke, C. D.; Goldberg, R. M.; Grothey, A.; Mooney, M.; Roach, N.; Saltz, L. B.; John, J. W.; William, A. W.; Meropol, N. J.
Article Title: KRAS and colorectal cancer: Ethical and pragmatic issues in effecting real-time change in oncology clinical trials and practice
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. © AlphaMed Press.
Keywords: cancer survival; treatment outcome; gene mutation; overall survival; proto-oncogene proteins; fluorouracil; advanced cancer; antineoplastic agents; clinical trials as topic; clinical practice; physician's practice patterns; colorectal cancer; progression free survival; receptor, epidermal growth factor; cetuximab; irinotecan; panitumumab; colorectal neoplasms; survival time; antibodies, monoclonal; folinic acid; predictive value of tests; medical society; medical oncology; metastasis potential; ras proteins; kras; oxaliplatin; k ras protein; medical ethics; b raf kinase; epidermal growth factor receptor antibody; clinical trials; ethics; clinical trial (topic)
Journal Title: The Oncologist
Volume: 16
Issue: 8
ISSN: 1083-7159
Publisher: Oxford University Press  
Date Published: 2011-07-07
Start Page: 1061
End Page: 1068
Language: English
DOI: 10.1634/theoncologist.2011-0011
PROVIDER: scopus
PUBMED: 21737577
PMCID: PMC3228147
DOI/URL:
Notes: --- - "Export Date: 3 October 2011" - "CODEN: OCOLF" - "Source: Scopus"
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  1. Leonard B Saltz
    790 Saltz