The inverted pyramid of biomarker-driven trials

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.