TY - JOUR
T1 - KRAS and colorectal cancer
T2 - Ethical and pragmatic issues in effecting real-time change in oncology clinical trials and practice
AU - Blanke, Charles D.
AU - Goldberg, Richard M.
AU - Grothey, Axel
AU - Mooney, Margaret
AU - Roach, Nancy
AU - Saltz, Leonard B.
AU - John, J. WELCH
AU - William, A. WOOD
AU - Meropol, Neal J.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - Clinical trials
KW - Colorectal neoplasms
KW - Ethics
KW - KRAS
UR - http://www.scopus.com/inward/record.url?scp=80052210041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052210041&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2011-0011
DO - 10.1634/theoncologist.2011-0011
M3 - Article
C2 - 21737577
AN - SCOPUS:80052210041
SN - 1083-7159
VL - 16
SP - 1061
EP - 1068
JO - Oncologist
JF - Oncologist
IS - 8
ER -