Abstract
Despite intense efforts, there are few lung cancer prevention trials showing positive results in the past few decades. Smoking cessation remains an important yet challenging public health issue. Multiple chemopeventive agents have been tested but, to date, there is none ready for clinical use and some even showed harmful effects in subgroups of subjects. To make progress, we need to learn from our past experiences and incorporate efficient designs in future trials. A few key areas will be reviewed and discussed in the presentation including the followings: (1) The success rate for large, randomized, phase III trials based solely on epidemiology data or retrospective analysis is low. (2) It is important to identify high-risk populations to increase the study efficiency. (3) Although several lung cancer risk models for predicting individual's cancer risk have been proposed, validation studies are needed to confirm their clinical applicability. (4) Similarly, markers for predicting lung cancer risks have been proposed but required independent validation. (5) Surrogate endpoints such as biomarker modulation are often used in prevention trials because it is often not feasible to use cancer development as the primary endpoint. However, surrogate endpoints are valuable only if they are associated with clinically meaningful endpoints. (6) Identification of prognostic and predictive markers for prevention can increase the study efficiency by stratifying subjects and focusing on the subgroups who are more likely to benefit. (7) Construct efficient designs for evaluating multiple preventive agents by applying adaptive designs to allow early stopping due to futility, efficacy, or equivalence, adding/dropping arms based on interim data, adaptive randomization to assign more patients to the more effective arms, seamless phase II/III studies, etc. In addition, evaluate the use of multistage designs to efficiently evaluate the treatment effect, identify important markers, and study the interaction between treatments and markers. (8) Screen preventive agents by using windows of opportunity trials with short term intervention and endpoints. (9) Encourage more randomized phase II trials and discourage lunching definitive phase III trial prematurely. (10) Develop a platform and modular clinical trial design approach for the development of preventive agents.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN07-05.
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