The Age of Personalized Oncology Therapies
Philadelphia, PA—The age of personalized cancer therapies is upon us. In oncology, personalized medicine encompasses the use of tests to determine the genes and gene interactions that can reliably predict an individual’s response to therapy or the chance of disease recurrence. The use of molecular diagnostic testing that provides the genomic profile of an individual’s tumor facilitates an understanding of some specific tumors that allows the selection of a treatment most likely to induce a response in that patient.
A session devoted to personalized oncology therapy examined its current and future role in cancer care and its impact on all oncology stakeholders.
A Broader Perspective Needed
Personalized oncology should be considered in a broader sense, incorporating not just genetic testing but also comorbidities and pharmacokinetic characteristics of patients, among other things, according to Gene Morse, PharmD, Professor and Associate Director, University at Buffalo, New York State Center of Excellence in Bioinformatics and Life Sciences.
Guidelines have attempted to introduce best practices into cancer care, but comorbidities can complicate guidelines implementation, Dr Morse said.
Another level of personalization is individualized drug dosing based on pharmacokinetic considerations (ie, renal and hepatic sufficiency), which is often omitted from personalized medicine approaches. “The use of therapeutic drug monitoring to individualize dosing…all of these technologies exist but are not really brought together in many therapeutic areas,” Dr Morse said.
The Human Genome Project has sequenced the full set of genes in the human body, but applying this information to personalized medicine has been difficult, because the genes’ relative expressions and their impact on disease recurrence must first be known before the tests can be useful.
Genetic Testing: A “Wild West” Situation?
About 1800 genetic tests are currently available and more are in development. Although genetic testing has generated a lot of enthusiasm, “I would consider it very experimental,” said Dr Morse. Some of these tests have solid evidence, but results from others vary from laboratory to laboratory. Similarly, gene-expression profiling is relatively new and unproven.
The concept of molecular tests, genomics, and proteomics is still mainly a research area, “yet, there are patients right now walking in for care, and these tests are being requested,” he said. “The payers may or may not want to have anything to do with these tests because the data are not there to support this.”
“It is a Wild West situation, where these tests are being developed with little regulatory oversight and have questionable clinical utility and a very uncertain impact on physician treatment choice. In other words, does the test influence what the physician is going to do? If the test isn’t going to change your treatment approach, why do the test?” said Gary L. Johnson, MD, MS, MBA, Medical Director, Humana, Clinical Leadership and Policy Development.
The economic value of many genetic tests is another area of uncertainty, said Dr Johnson, and incorporating these tests into clinical guidelines is in early stages.
Finding the best method to manage testing with these uncertainties is a challenge, he said. The options for managed care are to observe and eventually react, rely on external guidelines (that take a long time to develop), or develop in-house expertise. Another option is to look externally to organizations that act similarly to how a pharmaceutical benefits management company acts for pharmaceuticals.
“Our organization has chosen this last approach,” he said. “We partnered with a genomic testing management company that provides the evidence based policy development, in collaboration with our medical directors, both for the pharmaceuticals that we use and for the tests that are provided.” Pretest counseling and test interpretation counseling services are offered. In the future, Dr Johnson envisions “preferred” genomic tests similar to the preferred pharmaceuticals that are on many drug formularies.
The approach to oncology services at Premier Source Diagnostics is a patient-centric approach, said Perry Dimas, Vice President of Business Development, Premier Source Diagnostics, Orlando, FL.
“If the ordering physician finds that the test is medically necessary and he or she wants to order it, the patient should get it,” Mr Dimas said. Premier Source Diagnostics has mimicked the traditional specialty pharmacy model and applied it to molecular diagnostic tests. Physicians are offered no incentives (ie, reimbursement) to order a molecular test.
Molecular Testing Will Revolutionize Care
Molecular testing has the potential to revolutionize the way care is provided, said Richard Bender, MD, Clinical Professor of Medicine, UCLA School of Medicine, and Senior Vice President for Medical Affairs, Oncology, Caris Life Sciences (formerly Chief Medical Officer at Agendia).
In the case of chronic myelogenous leukemia, for example, treatment decisions depended on the absence or presence of Philadelphia chromosome– positive disease based on cytogenetic testing, which was costly and time-consuming, and it detected only large numbers of cells and not smallvolume disease.
“We now can detect tiny transcripts of the translocations and the genomic abnormalities…so we can monitor small numbers of residual tumor cells and determine very quickly whether our patient has responded to Gleevec or has responded to newer-class agents, how the mutations have developed, what the mutations are, and what drugs might be appropriate,” he said. “This has changed dramatically the way we practice healthcare.”
The evolution to molecular testing will allow for more uniform selection of systemic therapies. “I was delighted to hear that the National Compre hensive Cancer Network was going to be organizing a way to develop standards for how these kinds of tests are moved into the marketplace,” Dr Bender said. “You would be dismayed to know that organizations such as the College of American Pathology, which looks at all of our laboratories and sets standards for all of the tasks we do…have no standards for molecular testing.”
The reason for the absence of standards for molecular testing is that no method for developing proficiency exists, he said. Organizations that perform gene-expression profiling, for example, use their own tissues to set laboratory proficiencies. Therefore, it is “difficult for the industry to develop a standard. One of the things as an industry that we absolutely have to do is to have proficiency standards,” said Dr Bender.
Barrier to Molecular Testing: Medicare 14-Day Rule
A barrier to molecular testing is the Medicare 14-day rule. The rule states that any service rendered within 14 days of a hospital inpatient or outpatient admission must be billed directly to the hospital as part of the International Classification of Diseases, 9th Revision (ICD-9)-coded service. Therefore, a laboratory test must be performed outside the 14-day window for it to be paid as an outpatient test. The rule causes delays in test ordering, which is not in the best interest of the patient.
The Centers for Medicare & Medicaid Services (CMS) is starting a demonstration project in June 2011, lasting 24 months, in which it will investigate paying for certain complex diagnostic laboratory tests (ie, gene protein expression, genotyping, cancer chemotherapy sensitivity assay) outside the 14-day rule. Under the demonstration, independent and hospital- based laboratories may bill separately for demonstration tests that are ordered within a 14-day period after a hospital discharge.
“It will be up to us to demonstrate that this rule, within the CMS and other healthcare codes, needs to be changed,” said Dr Bender.
Changing the Translational Research Structure
Many companies are challenged by limited resources for research, preventing them from bringing their ideas to the level of approval, said Dr Morse. “We think the system should work with those companies and move those drugs and technologies forward,” he said. “There are a lot of good ideas, but the system doesn’t work well for people who can’t get the support from the venture capitalist.”
Establishing a translational practice– research–payer center interface can facilitate drug development and outcomes research programs. The introduction of healthcare informatics can help bridge drug development, clinical research, and nanopharmacology with translational science research and postapproval safety research (Figure), believes Dr Morse.
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“In Buffalo, for example, we’ve bridged our bioinformatics center, which is one of the largest computing clusters, with what will now be one of the largest HIPAA [Health Insurance Portability and Accountability Act]- compliant data centers, through a partnership with Dell,” he said.
Although the goal of healthcare informatics is to permit health and economics outcomes evaluations to guide clinical use and reimbursement policies, “the reality is that state by state, and region by region, the information technologies are at different stages of implementation,” said Dr Morse. “Even though we’d like to do that and that’s our vision, I think there’s a long way to go.”
Wise Resource Utilization Needed
In the process of extending the lives of cancer patients, more healthcare resources are being devoted to oncology care. “We need to use those resources wisely, and that’s the concept of value,” said Dr Johnson. “Our job in managed care is to be stewards of these generous but somewhat limited resources. We have a lot of treatment variability and we have a lot of outcome variability. It’s our job as the stewards of those resources to try to limit that treatment variability.”
The premise of marketing a test or drug to every patient is no longer valid, said Dimas. “We want the right patient to get the right drug or right test. It increases the value of that service,” he said.
Health plan reimbursement for personalized oncology therapies is currently unpredictable and variable. As new molecular or genotyping tests and personalized drugs come to market, affordability cannot be underestimated, said Dr Morse. Therefore, methods for applying them cost-effectively must be devised.