The optimal development of novel molecularly targeted agents for the treatment of cancer requires a re-evaluation of the current drug development paradigm. Selection of patients, optimal biologic dose versus maximum tolerated dose, definition of response and clinical benefit and trial designs that address these considerations are the focus of debate in the field of early cancer therapeutics. We present a review of the opportunities and challenges facing drug development in oncology through the phases of clinical development starting with first-in-human trials.
The design of trials to test molecularly targeted agents need to be revised to achieve objectives such as optimal biologic dose, which might require incorporation of analytically validated assays into initial clinical studies
The design of early phase trials of molecularly targeted agents might need to have end points such as progression-free survival or time to progression as opposed to objective response rate
The design of subsequent phase II studies will need to take into consideration the biological expectations of the molecular target agent (tumor shrinkage versus nonshrinkage)
Phase III studies should be pursued only in the presence of sufficient signs of activity, and ideally only initiated after randomized phase II studies of adequate power
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Gutierrez, M., Kummar, S. & Giaccone, G. Next generation oncology drug development: opportunities and challenges. Nat Rev Clin Oncol 6, 259–265 (2009). https://doi.org/10.1038/nrclinonc.2009.38
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