It was hoped some day that Genomic Analyses of cancer tumors would be able to identify in advance which patients will benefit from use of cancer drugs (clinical responders). A new draft report from the Agency for Healthcare Research and Quality (AHRQ) suggests that day is still a ways off.
The study looked at whether the presence of specific mutations in people who had breast and colon cancer and chronic myeloid leukemia determined if patients would respond to expensive new drugs commonly used to fight the diseases. Only in colon cancer did the mutation matter and in that case, while it ruled out the effectiveness of drug therapy, the relevant mutation only appears in a small percentage of cases.
In the finding most likely to cause controversy, the AHRQ report found there was "no consistent associations" between breast cancer patients with the relevant
CYP2D6 polymorphism and the outcome of tamoxifen therapy, whether as primary treatment or in as post-operative adjuvant therapy. Estimates vary, but anywhere from 10 to 40 percent of women have the gene variant of
CYP2D6 that is believed to slow the metabolism of tamoxifen and make it less effective. A number of companies sell a $300 test that can show if women have the allegedly telltale
CYP2D6 polymorphism.
As is often the case, the 13 studies identified by the systematic review didn't contain enough data to draw definitive conclusions. "Most studies were relatively small and thus underpowered to detect what would be a plausible effect size for the modification of response to tamoxifen by a single polymorphism," the report noted.
Numerous studies in recent years have noted that colon cancer patients with the
KRAS mutation do not respond to epidermal growth factor receptor inhibitors like cetuximab (Imclone Systems/Bristol Myers Squibb's Erbitux) and panitumumab (Amgen's Vectibix). The Food and Drug Administration, the European Medicines Agency and the American Society of Clinical Oncology have issued guidelines suggesting patients with the mutation shouldn't be given the drugs.
The AHRQ-sponsored review confirmed that finding. "Patients with
KRAS mutations were less likely to experience treatment benefit, compared to patients whose tumors were wild-type for
KRAS mutations," the report said. About 20 percent of patients have
KRAS mutations, which generally signal a more virulent form of the disease.
Chronic myeloid leukemia is one of the great success stories for targeted chemotherapy drugs and imatinib (Novartis' Gleevec) has been a godsend for patients with CML since it came on the market a decade ago. But resistance is growing, and at least two similar drugs are now on the market, dasatinib (Bristol-Myers' Sprycel) and nilotinib (Novartis' Tasigna).
Some mutations of the
BCR-ABL1 gene make the cancer resistant to imatinib (Gleevec), which is designed to block the action of the hyperactive tyrosine kinase receptors in people with CML. But don't look to any tests currently on the market to determine what they are. The review of 31 studies found that "the presence of any
BCR-ABL1 mutation does not appear to predict differential response to treatment in CML patients treated with imatinib-, dasatinib- (Sprycel), or nilotinib- (Nilotinib) based regimens."
Indeed, the report said there is "no evidence that presence of any
BCR-ABL1 mutation can differentiate response to tyrosine kinase inhibitor therapies."
"It is possible that pharmacogenetic (how our inherited genes affect the way we respond to drugs) testing and the subsequent use of targeted therapies will add cost without producing clinically meaningful improvements in patient outcomes," the report said.
http://www.ahrq.gov/clinic/ta/pharmgentest.pdf
Source: Gooznews on Health
There are some challenges in the development and practical use of pharmacogenomics. Many doctors now do not widely practice pharmacogenomics when treating patients since the field is still new.
Pharmacogenetic testing is also expensive, and insurance plans may not cover the costs of available tests. Researchers are working to develop more efficient and less expensive testing methods.
Although federal legislation has been passed that makes it illegal for companies and insurers to discriminate against people based on their genetic information, some ethical, legal, and privacy issues remain unresolved, which may affect the continued development of pharmacogenomics.
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