By Turna Ray
Testing colorectal cancer patients for their UGT1A1*28 status before prescribing irinotecan is cost-effective only when reduced doses of the drug are as effective as full doses in patients who are homozygous for the variant, according to a recent pharmacoeconomic study.
Published online in the American Cancer Society's journal Cancer, Taffet Gold et al. presented cost-effectiveness data based on a computer model following hypothetical patients with metastatic colorectal cancer treated with the FOLFIRI (5-fluorouracil/leucovorin with irinotecan) chemotherapy regimen.
All "patients" in this computerized, theoretical model first received a full dose of the drug. Then, the irinotecan dose was reduced by 25 percent in those patients revealed through genetic testing to have the UGT1AI*28 allele.
Irinotecan, marketed under the brand name Camptosar by Pfizer, is indicated as a first-line therapy for metastatic colorectal cancer when used as a component of the FOLFIRI regimen. Camptosar is also indicated for colorectal cancer patients whose disease has progressed or recurred following initial fluorouracil-based therapy. In 2005, the FDA altered the drug’s label to recommend oncologists screen patients for UGT1A1*28 alleles, which could make them more susceptible to neutropenia.
This dose reduction used by Taffet Gold et al. is discussed in the irinotecan revised irinotecan label by the US Food and Drug Administration.
"The current results indicated that pharmacogenetic testing for UGT1A1*28 variant homozygosity may be cost effective, but only if irinotecan dose reduction in homozygotes does not reduce efficacy," the study authors concluded in the Cancer paper. "Future studies to evaluate reduced-dose efficacy in homozygotes should be considered."
This kind of economic analysis can be useful in driving adoption of pharmacogenomic tests, as payors increasingly want to see clinical utility and cost-effectiveness analyses prior to reimbursing for such products.
In the study conducted by Taffet Gold et al., researchers found that pretreatment genetic testing saves $272 per patient and "slightly" improves quality-adjusted life expectancy (0.1 quality-adjusted day per patient tested, or approximately 2 quality-adjusted hours).
According to the authors, cost-effectiveness depended on how well the chemo regimen worked in patients after dose-adjustments based on genetic testing, and not necessarily on adverse event risk assumptions. Although the computer model-guided genetic testing helped avoid 84 cases of neutropenia and 4.4 deaths, it was not cost-effective to administer irinotecan unless lower-dose irinotecan worked nearly as well as the full dose of the drug.
“At a threshold of $100,000 per quality-adjusted life year, the therapeutic efficacy of irinotecan in homozygotes after dose reduction had to be 98.4% of full-dose efficacy for genetic testing to remain preferred," the researchers reported.
The researchers estimate that future studies to determine whether this efficacy level can be achieved have an "economic value" of $22 million.
In order to develop the computerized model, researchers derived test performance, chemo toxicity, and quality-of-life estimates from published literature and product labeling. Costs of treatment were taken from 2007 Medicare fee schedules.
The study was funded with grants from the American Cancer Society and the Agency for Healthcare Research and Quality through the Weill Cornell's Center for Education and Research on Therapeutics.
Third Wave, under a collaborative agreement with Genzyme, markets the Invader UGT1A1 Molecular Assay. The UGT1A1*28 allele is present in approximately 10 percent of the North American population.