University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Oncologist. 2011;16(8):1061-8. doi: 10.1634/theoncologist.2011-0011. Epub 2011 Jul 7.
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.
系统治疗使晚期结直肠癌（CRC）患者的中位生存时间延长了近四倍，几乎是最佳支持治疗的预期时间，这一结果是通过联合化疗和靶向生物制剂实现的。虽然后者可以包括抗表皮生长因子受体抗体，如西妥昔单抗和帕尼单抗，但我们现在有强有力的证据表明，携带突变 KRAS 的患者不会从这类药物中获益。然而，出于各种原因，接受 KRAS 数据的可靠性和重要性需要几年的时间。从小的回顾性 II 期研究的呈现和发表到广泛接受 KRAS 预测价值以及行为变化的时间线——特别是在晚期/转移性 CRC 中的正在进行的国家试验的修改、国家指南和实践模式的变化，以及对单克隆抗体的标签适应证的调整——是漫长的。在这篇评论中，我们讨论了关于 KRAS 状态和晚期 CRC 患者治疗的数据披露过程是否有效，以允许对正在进行的公开资助临床试验做出及时决策，以及这些决策是否合理和合乎道德。总体目标是强调关于临床试验结果早期披露以及新科学数据的审查和采用的经验教训，并提出未来处理类似情况的修改建议。
