Evidence for Treatment-by-Biomarker interaction for FDA-approved Oncology Drugs with Required Pharmacogenomic Biomarker Testing
Open Access
- 31 July 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 7 (1), 1-9
- https://doi.org/10.1038/s41598-017-07358-7
Abstract
For oncology drugs that were approved by the US Food and Drug Administration (FDA) and required pharmacogenomic biomarker testing, we describe 1) the use of enrichment (biomarker-positive patients) and a randomized controlled design by pre-approval trials and 2) the treatment-by-biomarker interaction. From the 137 drugs included in the FDA table, we selected the 22 oncology drugs with required genetic testing in their labels. These drugs corresponded to 35 approvals supported by 80 clinical studies included in the FDA medical officer reviews of efficacy. For two thirds of approvals (24/35, 69%), all clinical studies were restricted to biomarker-positive patients (enriched). Among the 11 remaining approvals with at least one non-enriched trial, for five approvals, the non-enriched studies were non-randomized. The treatment-by-biomarker interaction was statistically significant for three approvals and missing for two. Among the six approvals with a non-enriched randomized controlled trial, three featured a statistically significant treatment-by-biomarker interaction (p < 0.10), for an enhanced treatment effect in the biomarker-positive subgroup. For two thirds of FDA approvals of anticancer agents, the requirement for predictive biomarker testing was based on clinical development restricted to biomarker-positive patients. We found only few cases with clinical evidence that biomarker-negative patients would not benefit from treatment.This publication has 34 references indexed in Scilit:
- Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy?Genetics in Medicine, 2013
- Regulatory Review of Novel Therapeutics — Comparison of Three Regulatory AgenciesThe New England Journal of Medicine, 2012
- Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS studyAnnals of Oncology, 2011
- BCR-ABL mutation testing to predict response to tyrosine kinase inhibitors in patients with chronic myeloid leukemiaPLoS Currents, 2011
- Debating Clinical UtilityPublic Health Genomics, 2010
- Lapatinib Combined With Letrozole Versus Letrozole and Placebo As First-Line Therapy for Postmenopausal Hormone Receptor–Positive Metastatic Breast CancerJournal of Clinical Oncology, 2009
- Use of Archived Specimens in Evaluation of Prognostic and Predictive BiomarkersJNCI Journal of the National Cancer Institute, 2009
- The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP Working GroupGenetics in Medicine, 2009
- Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal CancerJournal of Clinical Oncology, 2008
- Chronic Myeloid LeukemiaThe New England Journal of Medicine, 1999