• Drug metabolism genetic variants that predict adverse reactions to the cancer drug irinotecan.

Many of the tests that are predictive of a therapeutic response (hereinafter, in this report, “predictive tests”) have regulatory approval and are the standard of care for certain cancer treatments. The breast cancer drug Herceptin, as well as the tests that indicate patients likely to respond to it, has been on the market since 1998 and has been used to treat half a million patients (Roche, 2008). More than 100,000 Oncotype Dx tests, a gene expression test that predicts a patient’s benefit from chemotherapy as well as breast cancer recurrence, have also been used to determine treatment planning since the test came on the market in 2004 (Genomic Health, 2009). About half of all estrogen-positive breast tumors in the United States are being evaluated with this preditive test, estimated Dr. Steven Shak of Genomic Health, the test’s developer. In addition, the UGT1A1 molecular assay has Food and Drug Administration (FDA) clearance for patients with colorectal cancer who are considering taking Camptosar (irinotecan), and tests for KRAS are approved by the European Medicines Agency (EMEA) to predict patients’ response to panitumumab and cetuximab therapy in colorectal cancer.1 Phase III clinical trials have recently confirmed the predictive value of EGFR mutations for response to gefitinib (Iressa) and erlotinib (Tarveva), leading the EMEA to announce its approval of gefitinib as a treatment for lung tumors that have activating EGFR mutations (AstraZeneca, 2009).

Predictive tests can be useful in health care because they often calculate an individual’s response to treatment better than other clinical indicators, said Dr. Bruce E. Johnson of the Dana-Farber Cancer Institute. For example, non-smoking women with a particular type of lung cancer are more likely to respond to erlotinib or gefitinib than other patients with lung cancer. Patients meeting these clinical characteristics have a median progression-free survival (PFS) of about 6 months, compared to a median PFS of less than 3 months in individuals without these clinical features. However, median PFS was nearly 15 months in individuals with EGFR mutations that predict response to erlotinib, versus only about 2 months in individuals without these mutations (see Figures 1a and 1b). Dr. Johnson and Dr. Rafael Amado of GlaxoSmithKline noted the importance of showing, with appropriately


A similar decision was made by the FDA shortly after the workshop.

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