Health
Genetic precision (ASCO annual meeting)
■ The trickle of discoveries that revolutionized cancer care is turning into a flood.
By Victoria Stagg Elliott — Posted July 21, 2008
The increasing use of genetic profiling -- in regard to patients and their tumors -- is enabling physicians to identify more accurately who is most likely to benefit from certain treatment options, according to several studies and panel discussions at the June meeting of the American Society of Clinical Oncology in Chicago.
"We're on the cusp of an explosion of data that needs to be interpreted into future clinical trials and possibly into our treatment plans," said Neal J. Meropol, MD, who was part of a clinical science symposium on personalized medicine. He directs the gastrointestinal cancer program at Fox Chase Cancer Center in Philadelphia.
On the treatment front, researchers are identifying the genes expressed by various tumors that may determine drug response. Scientists from the University Hospital Gasthuisberg in Leuven, Belgium, presented data on how various forms of the KRAS gene in colon cancer tumors respond differently to the monoclonal antibody Erbitux. This drug, in combination with the FOLFIRI chemotherapy regimen, decreased the risk of disease progression by 32% in patients whose tumors expressed the gene's normal version but had no effect on those with the mutant form.
"This study helps us to identify which patients are most likely to benefit from adding the drug to treatment," said Dr. Eric Van Cutsem, lead author and a professor at University Hospital Gasthuisberg.
This paper was one of several dozen investigating the gene's impact. The hope is to save patients from the side effects of a drug that may not provide much benefit and ensure its expense is money well-spent.
"We are in an exciting era of targeted agents," said Julie Gralow, MD, chair of ASCO's communications panel. "We have hundreds more in the pipeline, but they're expensive. We need to know who will benefit and who won't. How we are going to afford these drugs is by better selection of patients."
Bottom line: The number of anti-cancer drugs has increased, and costs have skyrocketed. But survival has not always improved. A paper in the July 22, 2004, New England Journal of Medicine, for instance, reported that the regimen described cost $30,675 for eight weeks and advocated making deliberate decisions about when to use it. Depending on the type of cancer it is used to fight, the addition of Erbitux to an anti-cancer regimen increases survival by an average of six weeks to three months. Experts suspect the improved ability to choose those candidates most likely to get the maximum additional life expectancy will make it more worthwhile. It also may mean that health system resources will not be used to pay for pricey medications that won't have much of an effect.
Supportive care insights
Genetic testing also is starting to make inroads in the supportive care arena and may lead to more effective use of erythropoietin, a controversial drug commonly used to treat chemotherapy-related anemia. The Food and Drug Administration added warnings to the label last year in response to data suggesting that this medication accelerated tumor growth and increased the risk of mortality. A study presented at this meeting found that whether a tumor grew in response to this drug depended on the amount of erythropoietin receptor messenger RNA it produces. "This may mean we can use erythropoiesis-stimulating agents in a targeted way," said Dr. Gralow, also associate professor of medicine at the University of Washington, Seattle.
Another study suggested that, for lung cancer patients, the existence of cytokine gene polymorphisms could determine the amount of pain and the effect of analgesics. A second paper presented at the same session documented the genetic differences that may increase the risk for venous thromboembolism.
"It's an exciting time in oncology. There's so many new drugs to treat the cancer, but there's more to treating the cancer than just shrinking the tumor," said Howard L. McLeod, PharmD, the official commentator on both papers after their presentation at a clinical science session. He directs the Institute of Pharmacogenomics and Individualized Therapy at the University of North Carolina, Chapel Hill. "These studies are a nice start."
Determining relevance
But while genetics is now a more important part of cancer care, questions are being asked about the relevance of testing for one of the more established markers. Data presented at last year's meeting noted that some patients with HER2-negative breast cancers could benefit from the same treatment given to those who test positive for this gene, thereby indicating that the answer may not be relevant. Experts said the evidence was not yet strong enough to end regular use of this kind of genetic assessment and that the findings may have more to do with inaccurate testing than a lack of influence of this gene.
"The presentations from a year ago left a lot of confusion but emphasized the importance of high-quality HER2 testing," said Dr. Antonio C. Wolff, who chaired the educational session, "HER2-Targeted Therapy: Why Bother Testing?" He is also associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore.
Concerns also are being raised about the amount of research funding. The American Medical Association promotes appropriate use of pharmacogenomics in drug development and clinical trials. But many experts worry that flat funding of the National Institutes of Health since 2004 is slowing the transition of novel gene science from the bench to doctors and patients.
"We have a growing backlog of genetic discoveries that are waiting to be turned into targeted therapies," said ASCO Immediate Past President Nancy E. Davidson, MD. "Progress against cancer requires a consistent commitment over time, and research is the best tool we have to fight the battle against cancer."
Adjusted for inflation in the Biomedical Research and Development Price Index, NIH's budget has declined 13%. The National Cancer Institute's budget has gone down by 12%.
