Nature reviews. Clinical oncology
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Advances in our understanding of cancer biology have led to the discovery of a spectrum of new therapeutic targets. However, despite remarkable progress in the identification and characterization of novel mechanisms of the oncogenic process, the success rate for approval of oncology drugs remains low relative to other therapeutic areas. ⋯ To maximize the effectiveness of these new strategies, close collaboration between academic, industry, and regulatory agencies will be required. In this Review, we highlight new approaches in preclinical and clinical drug development that will help accelerate approval of drugs, and aim to provide more-effective treatments alongside companion diagnostic tests to ensure the right treatment is given to the right patient.
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Modern oncology drug development faces challenges very different from those of the past and it must adapt accordingly. The size and expense of phase III clinical trials continue to increase, but the success rate remains unacceptably low. Adaptive trial designs can make development more informative, addressing whether a drug is safe and effective while showing how it should be delivered and to whom. ⋯ Longitudinal models of biomarkers (including tumor burden assessed via imaging) enable predictions of primary end points. Taking a Bayesian perspective facilitates building an efficient and accurate trial, including using longitudinal information. A wholly new paradigm for drug development exemplifying personalized medicine is evinced by an adaptive trial called I-SPY2, in which drugs from many companies are evaluated in the same trial--a phase II screening process.