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The inverted pyramid of biomarker-driven trials

Nature Reviews Clinical Oncology volume 8, pages 562–566 (2011)Cite this article

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Abstract

In the past, clinical phase I trials often suffered from low response rates and inadequate experimental drug doses. Over the past decade, however, phase I trials have evolved from simple dose-finding studies to trials that might provide clinically relevant therapeutic opportunities for patients with advanced-stage cancer for which no standard therapies are available. In the future, the routine use of modern technologies such as large-scale genome sequencing will help to unravel the specific biology of a patient's cancer. Such tools will expand our knowledge about genetic aberrations and might provide opportunities for the development of novel, molecular targeted therapies for patients with refractory cancer. Increasingly, the focus will likely turn from carrying out large randomized trials in unselected patients to conducting smaller biomarker-driven trials in selected patients with known molecular aberrations. We expect that these new strategies will enhance response rates as appropriate patients are targeted, therefore sparing those patients who are unlikely to benefit.

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Figure 1: In large, randomized trials with unselected patients a dilution phenomenon is usually observed, as only a small subset of patients benefit from the tested treatment.

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Acknowledgements

We thank Joann Aaron (The University of Texas MD Anderson Cancer Center, USA) for scientific editing of this article.

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Authors and Affiliations

  1. Departments of Investigational Cancer Therapeutics (A Phase I Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Ignacio Garrido-Laguna & Razelle Kurzrock

  2. Gastrointestinal Cancer Clinical Research Unit, Spanish National Cancer Research Center, C/Melchor Fernández Almagro 3, Madrid, 28029, Spain

    Manuel Hidalgo

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I. Garrido-Laguna researched the data for this article. All authors contributed to the discussion of content, writing, and editing/reviewing of this article before submission and during the editing process.

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Correspondence to Ignacio Garrido-Laguna.

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Garrido-Laguna, I., Hidalgo, M. & Kurzrock, R. The inverted pyramid of biomarker-driven trials. Nat Rev Clin Oncol 8, 562–566 (2011). https://doi.org/10.1038/nrclinonc.2011.113

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