Precision Medicine: Precisely Where Are We Really?


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John F. Smyth, MD

Both the medical profession and the public at large need to be educated about the concept of iterative drug development with the goal of developing more precise medicines in a shorter time frame—but with an altered benefit/risk concept, which will be modified over time.

—John F. Smyth, MD

Having attended ASCO Annual Meetings for almost 40 years, I believe that this year’s 50th anniversary celebration was one of the best ever. In many of the presentations and discussions, I experienced a sense of reality about the true state of cancer management that in previous years has sometimes been overshadowed by excitement for novelty, exaggeration of findings, and a sense of forced optimism created by a demanding public and threatened finances.

Complex Problem

Of course, there should always be excitement—and you cannot pursue oncology unless you are essentially an optimist. But I was greatly encouraged by the open and frank appraisals of some of the huge challenges that we still face in improving the outcome of cancer treatment.

Nowhere was this more apparent than in the realm of “personalized medicine,” now known as “precision medicine”—in my opinion, a much more appropriate term. The speed of advancement in our knowledge of the genetic detail of individual tumors and of their patient host is truly astonishing. That progress is undeniably exciting, but we must realize that the more we know, the greater the complexity of the problem.

And the more we “individualize” the problem, the harder it becomes to define personalized prescriptions for management. Where once we thought that cancers such as breast, colon, lung, and melanoma could be subdivided by pathologists into a small number of subsets, we now appreciate an ever-increasing diversity within these pathologic groupings. Why does this matter?

Several Concerns

There are several concerns, and foremost among them is this: the public may think that we can already apply this new knowledge to offer much more specific or precise treatments. That of course is the goal, but we have not yet reached it.

Two of the greatest challenges concern the validity of the genetic testing on which subsets are defined, and the dilution factor of having smaller numbers in a specific category within clinical trials. If we are going to depend on genetic profiling in order to develop and assign more precise medicines, then we have to improve the quality assurance of the myriad genetic platforms currently in use, and this has to be regulated.

The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) are conscious of this requirement and will need robust reassurance if they are to approve new products based on much smaller patient groupings in pivotal trials—a direct consequence of splitting cancers from, say, two types of breast cancer into 12, or event malignant melanoma into two different categories, depending on wild-type or mutant BRAF, for example.

Real Progress

Real progress is being made between the drug development community and regulators to address these issues, and the EMA’s recent announcement about Adaptive Licensing confirm their wish to have a realistic dialogue with industry and academia. They make it clear that this will be an iterative process to speed up the whole drug development process, hopefully to achieve the goal of offering more precise treatment to individuals.

If, however, they are able to release new drugs on the market earlier than at present, then the medical profession must respond to control off-label uses, and the public must be educated to understand the issues around benefit/risk if clinical trials are smaller and therefore the database less robust.

At ASCO 2014, I did not hear any particularly encouraging comments about the costs of cancer care. In theory, if we use genomics to speed up drug development and improve efficiency by selecting the most appropriate patients for any given medicine, then the costs of that medicine should be reduced. Companies argue that the additional testing required—for example, companion diagnostics—outweigh any such cost reduction. I am not holding my breath, but as I say, to be an oncologist you must remain essentially an optimist.

Take-Home Message

In summary, one of the important take-home messages I took from the Annual Meeting was that precision medicine is moving at a really exciting, if challenging, pace. We have to address specific issues about the quality assurance of genomic platforms, and we have to work with licensing authorities to give confidence around smaller pivotal trials. Both the medical profession and the public at large need to be educated about the concept of iterative drug development with the goal of developing more precise medicines in a shorter time frame—but with an altered benefit/risk concept, which will be modified over time. ■

Disclosure: Dr. Smyth reported no potential conflicts of interest.

 



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