Amgen's Vectibix scrutinized. Credit: c40/ZUMA Press/Newscom

A new US government–sponsored report on three pharma-cogenetic tests for targeted cancer treatments has confirmed the usefulness of KRAS testing but raised doubts about two other widely adopted tests. The Agency for HealthCare Research and Quality (AHCRQ) commissioned the report at the request of the Centers for Medicare and Medicaid Services (CMS) to help set clinical guidelines and reimbursement policies. The report, produced by researchers at the Tufts Evidence-Based Practice Center, Boston, examined published studies linking KRAS mutations and the ability to predict responses to two colorectal cancer antibody therapies: Erbitux (cetuximab) from Bristol-Myers Squibb and ImClone, and Vectibix (panitumumab) from Amgen. The team also analyzed studies of genetic variants in CYP2D6 (cytochrome P450) as response predictors to AstraZeneca's breast cancer drug Nolvadex (tamoxifen); and studies of BCR-ABL1 mutations as response predictors to Novartis's Gleevec (imatinib) and Bristol-Myers Squibb's Tasigna (nilotinib) in leukemia treatments. The report's conclusion affirmed the value of KRAS testing in colorectal cancer therapies but found no evidence for consistent associations between BCR-ABL1 status and response to tyrosine kinase inhibitor treatment or CYP2D6 polymorphism status and response to Nolvadex. Mark Ratain, director of the Center for Personalized Therapeutics at the University of Chicago and one of the report's official reviewers, expressed outrage at the CYP2D6 finding. “This [analysis] is a tremendous disservice to taxpayers and patients,” he says. “Medco [pharmacy services firm] is testing all their patients and I would never order this drug without a test.” Nolvadex is a pro-drug, and “strong laboratory evidence” exists that individuals with certain CYP2D6 genotypes cannot metabolize it properly, Ratain notes. According to Ratain, the original version of the report did not reference the largest study by far on CYP2D6 testing (JAMA 302, 1429–1436, 2009) and “lumps bad studies with good ones.” The report's conclusions could encourage more widespread use of KRAS tests. But Grace Wang from the Centers for Translational and Policy Research on Personalized Medicine at the University of California, San Francisco, says it might make it harder to get reimbursement for CYP2D6 and BCR-ABL1 testing. Overall, she notes, “The report really highlights what we don't know” about the benefit and harms of testing.