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 decisions 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.
authors: University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada. cblanke@bccancer.bc.ca
authors: Charles D
authors: CD
authors: Blanke
authors: Richard M
authors: RM
authors: Goldberg
authors: Axel
authors: A
authors: Grothey
authors: Margaret
authors: M
authors: Mooney
authors: Nancy
authors: N
authors: Roach
authors: Leonard B
authors: LB
authors: Saltz
authors: John J
authors: JJ
authors: Welch
authors: William A
authors: WA
authors: Wood
authors: Neal J
authors: NJ
authors: Meropol
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068818:Cetuximab; D002986:Clinical Trials as Topic / Q000941:ethics*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000276:immunology; D006801:Humans; D008495:Medical Oncology / Q000941:ethics; D000077544:Panitumumab; D010818:Practice Patterns, Physicians' / Q000941:ethics*; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077544:Panitumumab; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab