This strategy is acceptable only in cases where investigators have already enough evidence to completely rule out the efficacy of the experimental treatment in M- patients. Due to the absence of M- patients, targeted design allows investigators to avoid

potential dilution of the results. A third approach is the so-called “” strategy design “”. According to this design, the experimental arm will receive a personalized treatment based on the status of predictive marker, while all patients assigned to the control arm receive standard treatment. A great limit of strategy design is related to the proportion of M+ patients on the Akt inhibitor overall number of patients. If M+ patients are a small minority, treatment received will be nearly the same in both arms, and the study will provide little information on the efficacy of experimental treatment. On the contrary, the strategy design will be particularly effective when both M+ and M- patients represent a significant proportion of the patients. Conclusion The success of a targeted drug development (and the patient benefit) strongly depends

on extensive pre-clinical and early clinical modeling, and so depends on conducting good science. Early phases, and in particular phase II studies, remain crucial for development of targeted drug, because this is the moment in which it is possible to explore surrogate and potential selection biomarkers. With these Mdm2 inhibitor intents, phase II trials should be hypothesis-generating and should signal either to progress to phase III, and to go back to the lab. How clinical trial design with molecularly targeted

agents should be improved and fasten to realize the real ‘bench to bedside’ medicine? Molecularly targeted agents should be studied with those early phases with the newest adaptive design [17], with a more realistic basic hypotheses [33], and be ‘tailored’ on a clearly specific molecular feature or signaling [34]. This pivotal process, will come up into more accurate early studies, providing few positive studies but with stronger and more reliable results. Few drugs will enter the phase III fashion, by increasing the chance to win over the standard. These following phase III trials (which remain always mandatory), will be able to test Sulfite dehydrogenase more frequently superiority hypotheses, providing big differences, less patients to be enrolled, into shorter time for completing the studies. Acknowledgements Supported by a grant of the National Ministry of Health and the Italian Association for Cancer Research (AIRC). References 1. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L: Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005, 353: 123–132.CrossRefPubMed 2.