title: Pharmacogenomics in early-phase oncology clinical trials: is there a sweet spot in phase II?
abstract: Many clinical trials of oncology drugs now include at least a consideration of pharmacogenomics, the study of germline or acquired genetic factors governing a drug's response and toxicity. Besides the potential benefit to patients from the consideration of personalized pharmacogenomic information when making treatment decisions, the incentive is clear for oncology drug developers to incorporate pharmacogenomic factors in the drug development process, because pharmacogenomic biomarkers may allow predictive characterization of subpopulations within a disease that may particularly respond or may allow preidentification of patients at highest risk for adverse events. There is, however, a lack of agreement in actual practice about at what point in the oncology clinical drug development process pharmacogenomic studies should be incorporated. In this article, we examine the recent growth of pharmacogenomics in oncology clinical trials, especially in early-phase studies, and examine several critical questions facing the incorporation of pharmacogenomics in early oncologic drug development. We show that phase II clinical trials, in particular, have a favorable track record for showing positive pharmacogenomic signals, worthy of additional follow-up and validation, and that the phase II setting holds significant promise for potentially accelerating and informing future phase III trials. We conclude that phase II trials offer an ideal "sweet spot" for routine incorporation of pharmacogenomic questions in oncology drug development.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, and Comprehensive Cancer Center Pharmacogenomics and Experimental Therapeutics Program, The University of Chicago, Chicago, Illinois, USA. podonnel@medicine.bsd.uchicago.edu
authors.forename: Peter H
authors.initials: PH
authors.lastname: O'Donnell
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D006801:Humans; D008495:Medical Oncology; D009369:Neoplasms / Q000188:drug therapy; D010597:Pharmacogenetics / Q000379:methods*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents