EMCC: Personalized Medicine May Prove Faster and More Effective

News from the European Multidisciplinary Cancer Congress (EMCC) continues to reinforce the idea that with personalized medicine focusing on patient subpopulations, smaller, faster trials may improve cancer patient survival and facilitate availability of new treatments.

At a drug development session on Monday September 26, Dr. Marie-Cecile Le Deley, associate professor of clinical epidemiology and biostatistics at the Institut Gustave-Roussy in Villejuif, France presented trial results that hint that smaller, faster trials can improve cancer patient survival. With the oncology community's goal of substantially personalizing medicine, this type of research can be invaluable to direct efforts to focused and smaller clinical trials.

Dr. Le Deley and colleagues at the Mayo Clinic in Rochester, Minnesota simulated a series of two-treatment superiority trials in which a novel treatment was compared to standard of care over a span of 15 years. Different parameters, such as the criteria used to adopt a novel therapy as a new standard and the number of trials performed, were tested. The simulation studies were used to estimate the survival improvements that could be expected for different drug development strategies. The conclusion of the research was that "as patient populations become more specific (and thus smaller), the current risk-averse trial design strategy may slow long-term progress and deserves reexamination."

"We found that there were important gains in survival attributable to a strategy of conducting more trials with smaller sample sizes and relaxed evidential criteria compared with those required under traditional trial designs," said Dr. Le Deley. "The downside of this approach is that we also reduce the certainty of the findings: we might select as a new temporary standard a treatment that does not work better than the existing best therapy, but the fact that we will conduct many more trials will allow such errors to be quickly remedied," she added.

Dr. Le Deley also expressed her opinion that because novel targeted agents generally have fewer safety issues compared with older cytotoxic treatments that kill cells, the risk of accepting a few therapies that offer no benefit seems reasonable. This view is based on the fact that while large sample-size clinical trials have a high statistical power, they take a very long time to reach a definitive result, especially when a disease is rare and trial accrual may be small. Additionally, these trials randomize patients to a control arm for a prolonged period of time without the ability to cross over into a more active treatment arm.

Generally, regulatory agencies and statisticians are risk-averse owing to the fact that a lower-risk strategy has a lower probability of reaching a wrong conclusion. The recommendation that trials should have a smaller sample size and more relaxed decision criteria only makes sense if there is no way to increase the trial accrual rate, stresses Dr. Le Deley. Traditional large-scale trials are still needed but smaller, quicker trials should be done when appropriate. The results of the research presented show that these will lead to quicker results, and in the long term have the potential for greater patient gains. In the context of the large number of new treatments being designed for specific molecular targets, smaller, faster trials will allow for more efficient answers regarding whether a therapy is efficacious.

As oncology becomes increasingly entrenched in the personalized medicine era, clinical trial design and interpretation will have to evolve, pointed out Professor Michael Baumann, President of the European Cancer Organisation in response to the research results. An open dialogue among researchers, policy makers, and regulatory agencies is therefore essential.