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Strategies to Overcome the Challenges of Personalized Medicine

August 2013 Vol 6, No 6 Special Issue

Chicago, IL—The use of molecular profiling to guide treatment decisions is envisioned as a critical new strategy in cancer therapy, but for patients to reap the benefits of personalized medicine, sweeping reforms are needed in how genetic information is analyzed and acted upon, said Richard L. Schilsky, MD, Chief Medical Officer, American Society of Clinical Oncology (ASCO), and Chief of Hematology/Oncology, Department of Medicine, University of Chicago Comprehensive Cancer Center, IL.

Dr Schilsky’s talk at ASCO 2013 was titled, “Breaking Down Barriers in the Implementation of Personalized Medicine.”

“We have learned that each person’s tumor has a unique molecular profile. This has generated excitement, but difficulty as well, with respect to how we understand the unique biology of each tumor and how we act on this to individualize treatment,” he noted.

Challenges in Personalizing Treatment
Implementing a personalized cancer medicine program requires (1) adequate tumor tissue available for molecular profiling; (2) a standardized, high-quality laboratory for molecular profiling to ensure the accuracy, reliability, and timeliness of test results; (3) identification of tumor “targetable” molecular aberrations; and (4) the availability of a targeted agent known to inhibit the activity of the molecular aberration.

There are problems inherent in all of these steps. Established guidelines for tissue collection and testing are lacking, while testing facilities are proliferating. “Clinicians are having a hard time figuring out which lab to use, which gives the most reliable results. And there are few established standards for the molecular workup of tumors,” Dr Schilsky said.

Dr Schilsky proposed that ASCO and the College of American Pathologists collaborate on developing guidelines for tissue handling and molecular workup. Guidelines established by professional societies will ensure that laboratories across the country meet uniform proficiency standards and produce high-quality results.

But there will still be the problem of the increasing complexity of molecular diagnoses, he added. “The problem is, the harder you look, the more you will find,” Dr Schilsky said. “We are moving from individual mutations to multiplex assays of mutations of interest to whole genome and whole exome sequencing.”

Then, there is the problem of using the information that is obtained. Physicians need standardized decision support tools so that they can understand the mutational profiles identified on these tests and how to apply the information in treatment.

“For the oncologist, the challenge is understanding what mutations are clinically ‘actionable’ and which are not—which can be acted on and which ignored, and what treatment may be the best match for the molecular profile of the tumor,” Dr Schilsky said.

Drug access is also a big problem. The test result will most likely suggest that the best course of action involves the off-label use of an available agent or an experimental drug that can only be accessed through a clinical trial or from the manufacturer.

National Registry
Dr Schilsky proposed the establishment of a national registry in which baseline and outcomes data could be aggregated. This would be a way to make sense of the genetic information on a grand scale and to move personalized medicine forward on the individual level. The registry would record information about molecular test results, clinical decisions that are made based on the genetic information, and patient outcome.

“My Cancer Genome, which was developed at Vanderbilt, is very useful. It collates all the available medical literature to inform the doctor as to whether an aberration in a particular tumor might be clinically meaningful. But the problem is that it’s collated from the literature, and it’s about what might work. It does not include the actual outcomes for that particular approach, for that particular aberration, in that particular patient,” he said.

National Pharmacy Exchange
Dr Schilsky’s solution to the problem of access to cancer drugs is a national pharmacy exchange that contains targeted agents against common mutations, as well as the treatments administered and their outcomes. This national pharmacy exchange would work in this way:

  • The patient is enrolled into the national registry
  • The physician submits a validated test result from a certified laboratory, along with a request for the matched drug
  • The formulary committee reviews the request against predetermined guidelines; if approved, the pharmacy dispenses the drug
  • The patient receives the drug and the clinical outcomes are entered into the registry.

“For this to work, all stakeholders must participate,” Dr Schilsky emphasized. “Private insurers and the Centers for Medicare & Medicaid Services must agree to reimburse for the treatment cost.”

Such a system would benefit patients, who would receive a matched targeted agent; physicians, because they would receive guidance, treatment recommendations, and access to drugs for their patients; the pharmaceutical industry, because companies would obtain data on drug use and outcomes to inform their research and development, as well as the life cycle management for their drugs; insurers, because they would receive data to inform coverage decisions (eg, off-label use); and regulators, such as the US Food and Drug Administration, because they would receive real-world outcomes and safety data.

Only 5% of patients participate in clinical trials, and it is becoming clear that drugs will need to be evaluated outside of this traditional framework, Dr Schilsky said. “There are too few patients, too many molecular subtypes, too many drugs to study, and not enough time or money. We must find alternative ways to learn about patients.”

Last modified: August 30, 2021