Systematic Reviews on Selected Pharmacogenetic Tests for Cancer Treatment: CYP2D6 for Tamoxifen in Breast Cancer, KRAS for anti-EGFR antibodies in Colorectal Cancer, and BCR-ABL1 for Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia. Technology Assessment Report

摘要

The challenges in the integration of cancer pharmacogenetics and targeted therapies in clinical practice should require evidence of benefit to the patients (a favorable balance of harms and benefits of testing), cost-effectiveness for the healthcare system, incorporating patient preferences, improving provider education, and anticipating potential ethical and social implications. It is possible that pharmacogenetic testing and the subsequent use of targeted therapies will add cost without producing clinically meaningful improvements in patient outcomes. In the absence of data that can address its clinical utility and value, integration of pharmacogenetic testing in the healthcare system is not straightforward. This Technology Assessment assesses the evidence on the benefits and harms of three pharmacogenetic tests employed for three different diseases pertinent to the Medicare beneficiary population: variations in CYP2D6 and response to tamoxifen in breast cancer; variations in KRAS and response to cetuximab and panitumumab in colorectal cancer and variations in BCR-ABL1 and response to imatinib, dasatinib and nilotinib in chronic myeloid leukemia. The authors performed three systematic reviews of the published literature to address the following Key Questions for each of the aforementioned topics: (1) Does the genetic test result predict response to therapy. (2) What patient- and disease-related factors affect the test results, their interpretation or their predictive response to therapy. (3) How does the gene testing impact the therapeutic choice. (4) What are the benefits and harms or adverse effects for patients when managed with gene testing.