New Kind of Trials
Studying targeted medicines in traditionally defined patient populations is quite problematic. For example, if we want to test a medicine like gefitinib, we do not need patients who are clinically diagnosed with non-small cell lung cancer, but patients with a specific EGFR mutation. If we were to test the medicine on a population which is not preselected for the presence of the mechanism in question, we might conclude that the medicine does not have an appropriate benefit-risk ratio. However, if tested on patients with the underlying mechanism we might come to the opposite conclusion. Gefitinib is therefore indicated for patients with tumours showing specific EGFR mutations, while it is irrelevant whether the tumour is located in the lungs.
In order to develop targeted medicines, patients will have to be selected based on presence or absence of specific biomarkers. In some situations, that may be a relatively small subset of the traditionally defined patient population.
For instance: traditionally we would test a drug on patients with breast cancer. But now we would select patients with a similar disease pathway: e.g. Her-2 positive. Eventually, the patient population may be extended: it is to be expected that we can treat patients with malignant tumours in other organs with the same medicine, because the tumours are caused by the same molecular mechanisms (e.g. m-TOR mutations).
With this approach, patient populations participating in clinical trials can be smaller, or at least much more homogenous, and response to treatment will be more consistent and predictable as well.