Nature Reviews Clinical Oncology is proud to feature a Focus on clinical trials. The April 2012 issue includes discussion on the recent and ongoing challenges of undertaking clinical trials in patients with cancer. This special issue comprises four Reviews and two Perspectives by key opinion leaders in the field.
Image : Getty (adapted).
EDITORIAL
Oncology trials—the elephant in the room
Rebecca Kirk & Lisa Hutchinson
doi:10.1038/nrclinonc.2012.33
Nature Reviews Clinical Oncology 9, 185-186 (2012)
REVIEWS
Adaptive clinical trials in oncology
Donald A. Berry
doi:10.1038/nrclinonc.2011.165
Nature Reviews Clinical Oncology 9, 199-207 (2012)
The size, length and cost of phase III clinical trials are prompting oncology researchers and pharmaceutical companies to look for other options. This Review outlines adaptive clinical trial designs that can address many questions at once. 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 study and are matched with their biomarker signatures.
Role of randomized phase III trials in an era of effective targeted therapies
Manish R. Sharma & Richard L. Schilsky
doi:10.1038/nrclinonc.2011.190
Nature Reviews Clinical Oncology 9, 208-214 (2012)
If a targeted therapy demonstrates convincing efficacy in early clinical testing, can randomized phase III trials be avoided? Sharma and Schilsky discuss when it is reasonable to consider foregoing randomized phase III trials before drug approval and also highlight the caveats. They explore the consequences of such an approach and propose criteria that the drugs must meet to be approved without a phase III trial.
Drug development and clinical trials—the path to an approved cancer drug
Eric H. Rubin & D. Gary Gilliland
doi:10.1038/nrclinonc.2012.22
Nature Reviews Clinical Oncology 9, 215-222 (2012)
The current system for the development of anticancer drugs is not fit for purpose. In this Review article, this system is examined from the perspective of the drug company, offering a fresh look at development from target identification up to registration.
Use of neoadjuvant data to design adjuvant endocrine therapy trials for breast cancer
Rodrigo Goncalves, Cynthia Ma, Jingqin Luo, Vera Suman & Matthew James Ellis
doi:10.1038/nrclinonc.2012.21
Nature Reviews Clinical Oncology 9, 223-229 (2012)
Is there a precise end point that could enable us to compare neoadjuvant and adjuvant endocrine therapy outcomes? A reliable short-term surrogate to assess the potential of endocrine drugs in the adjuvant setting? In this Review, Goncalves et al. summarize the studies in which the proliferation marker Ki 67, measured during neoadjuvant treatment, has predicted accurately and consistently the results of much larger studies in the adjuvant setting.
PERSPECTIVES
Hurdles in anticancer drug development from a regulatory perspective
Bertil Jonsson & Jonas Bergh
doi:10.1038/nrclinonc.2012.14
Nature Reviews Clinical Oncology 9, 236-243 (2012)
In terms of drug development, the main driving force should be optimized benefit–risk to patients; however, no drug can be of real benefit unless it has achieved approval from the regulatory agencies. This Perspectives allows us a peek behind the door of one of those agencies (EMA) and outlines the hurdles that exist and that need to be overcome before we can have an efficient, biomarker-driven drug development program. Points for discussion in the community are raised and suggestions are put forward.
Equipoise: asking the right questions for clinical trial design
Steven Joffe & Franklin G. Miller
doi:10.1038/nrclinonc.2011.211
Nature Reviews Clinical Oncology 9, 230-235 (2012)
Randomized controlled trials (RCTs) pose dilemmas in terms of the tension between the therapeutic obligations of the physician and the scientific obligations of the investigator. Clinical equipoise is often regarded as a solution to this problem. The authors critically evaluate clinical equipoise and highlight its flaws as an ethical requirement for RCTs and propose an alternative method of risk–benefit assessment.
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