Chutes and ladders on the critical path:comparative effectiveness, product value, and the use of biomarkers in drug development.

摘要

On 16 December 2008, the US Food and Drug Administration (FDA) held a meeting of the Oncologic Drugs Advisory Committee to discuss proposals for label changes for the epidermal growth factor receptor (EGFR)-targeting cancer drugs cetuximab (Erbitux, ImClone Systems) and panitumumab (Vectibix, Amgen). The drugs' manufacturers presented retrospective data on genetic testing (using a variety of assay techniques) for somatic mutations in the KRAS gene in the tumors of patients with colorectal cancer who had been enrolled in clinical trials. In multiple retrospective subgroup analyses, patients identified as having mutated KRAS genes failed to respond to these therapies. This result is biologically plausible because KRAS mutations in tumors often result in constitutive activation, and KRAS is downstream in the EGFR signaling pathway.