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* COMMENT * 28 November 2018 The development of oncology drugs traditionally begins by studying them in heavily pretreated patients, and then working ‘upstream’ to populations with

earlier-stage disease. The recent FDA approval of an androgen receptor antagonist first in prostate cancer patients without demonstrable metastatic disease but at high-risk for metastasis,

based on a novel metastasis-free survival end point developed by the FDA, could provide a template for a paradigm shift. By * William N. Hait * External Innovation, Johnson & Johnson,

New Brunswick, NJ, USA. * Peter F. Lebowitz * Janssen Oncology, Janssen Research and Development, Spring House, PA, USA. Traditionally, oncology drugs are first studied and approved in

patients with advanced, heavily pretreated cancers, and then in patient populations with earlier stages of disease. This is an efficient route for bringing a new drug to patients for several

reasons. First, the size of studies can be smaller because studies may not require an active comparator arm if no approved drug is available for the indication. Second, the study duration

can be shorter in late-stage disease because progression events typically occur rapidly in this setting, which decreases the time to reach a pre-specified end point. Third, patients with

advanced, heavily pretreated disease tend to be actively looking for clinical trials, which can lead to rapid enrolment. ACCESS OPTIONS Access Nature and 54 other Nature Portfolio journals

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Reviews Drug Discovery_ 18, 159-160 (2019) _doi: https://doi.org/10.1038/d41573-018-00006-3_ REFERENCES * Beaver, J. A., Kluetz, P. G. & Pazdur, R. Metastasis-free survival – a new end

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Article  PubMed  Google Scholar  Download references COMPETING INTERESTS W.N.H. is an employee of J&J and former head of Janssen R&D. P.F.L. is an employee and stockholder of

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