It is estimated that around 400 new drug therapies in the pipeline will soon be available for testing in cancer clinical trials. As a result a major focus of ASCO is on designing the best clinical trials, and selecting the right patients for each. In individual tumor trials, it has been seen that some patients respond to a drug, while others don’t. Genetics likely plays a key role in determining this, and for example in colon and breast cancer trials, patients are now enrolled on the basis of their genetic mutation type. This has led to the evolving field of ‘personalized medicine’, where drug regimes will be tailored for individual patients. As one example, a patient’s response to drugs might be determined in part by the level of insulin or insulin-like growth factor (IGF1) in blood. Insulin/IGF1 levels are high in obesity and Type 2 diabetes, and both of these groups are in general more likely to develop tumors and within clinical trials are less likely to be responsive to targeted tumor drug therapies. This makes biological sense – insulin/IGF1 binding to the cell stimulates Akt signaling- and Akt is a well-recognized candidate drug target for many tumors (including neurofibromatosis). Interestingly cancer incidence is reduced overall in people taking metformin – an insulin sensitizing drug that reduces the amount of circulating insulin/IGF1 in the blood. For some patients, metformin may have some potential in planning and conducting cancer trials.
Prioritizing and evaluating cancer drug therapies will require clinicians to partner with multi-disciplinary teams spanning biology to regulatory issues. This will also require that the right endpoints be used for clinical trials so findings can be properly interpreted. Some sophisticated trial models are underway, with multiple ‘arms’ (patients treated under different drug combinations). Also there has been a move recently toward surrogate endpoints, measures that allow a trial to be shortened so a go/no go decision can be made earlier. However its important these are still meaningful. Given the dizzying number of clinical trials presented at ASCO, it is not surprising there was a cautionary note from one speaker not to over-interpret small individual studies too soon, but to consider the case for doing large population based studies with more emphasis being placed on long term monitoring of drug effects.
