Clinical trial designs incorporating predictive biomarkers.

Cancer Treat Rev
Authors
Keywords
Abstract

Development of oncologic therapies has traditionally been performed in a sequence of clinical trials intended to assess safety (phase I), preliminary efficacy (phase II), and improvement over the standard of care (phase III) in homogeneous (in terms of tumor type and disease stage) patient populations. As cancer has become increasingly understood on the molecular level, newer "targeted" drugs that inhibit specific cancer cell growth and survival mechanisms have increased the need for new clinical trial designs, wherein pertinent questions on the relationship between patient biomarkers and response to treatment can be answered. Herein, we review the clinical trial design literature from initial to more recently proposed designs for targeted agents or those treatments hypothesized to have enhanced effectiveness within patient subgroups (e.g., those with a certain biomarker value or who harbor a certain genetic tumor mutation). We also describe a number of real clinical trials where biomarker-based designs have been utilized, including a discussion of their respective advantages and challenges. As cancers become further categorized and/or reclassified according to individual patient and tumor features, we anticipate a continued need for novel trial designs to keep pace with the changing frontier of clinical cancer research.

Year of Publication
2016
Journal
Cancer Treat Rev
Volume
43
Pages
74-82
Date Published
2016 Feb
ISSN
1532-1967
URL
DOI
10.1016/j.ctrv.2015.12.008
PubMed ID
26827695
PubMed Central ID
PMC4737867
Links
Grant list
KL2 TR000136 / TR / NCATS NIH HHS / United States
R01 CA174779 / CA / NCI NIH HHS / United States