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Pharmacogenetic Testing for Oncology Drugs and Targeted Therapy
Pharmacogenetic Testing for Oncology Drugs and Targeted Therapy
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5%<br />
CYP450 Population Distribution*<br />
14%<br />
51%<br />
FOCUS POINTS<br />
ONCOLOGY DRUGS AND<br />
T A R G E T E D T H E R A P Y<br />
Using KRAS testing to select patients for EGFR inhibitor therapy saved $7,500-<br />
$12,400 per patient in the United States and €3,900-€9,600 per patient in<br />
Germany with equivalent clinical outcomes. (Vijayaraghavan et al., 2012)<br />
CYP2D6<br />
Ultrarapid Metabolizer (UM)<br />
Extensive Metabolizer (EM)<br />
Intermediate Metabolizer (IM)<br />
Poor Metabolizer (PM)<br />
30%<br />
*Proprietary Indian data | All rights reserved with Datar Genetics Limited | Publication in process<br />
Cost-effectiveness of thiopurine methyltransferase (TPMT) genotyping in<br />
pediatric acute lymphoblastic leukemia (ALL) patients was calculated as $2700<br />
per life-year gained. (van den Akker-van Marle et al., 2006)<br />
US FDA recommends Pharmacogenetic testing for more than 40 Oncology Drugs.<br />
38%<br />
40%<br />
40%<br />
43%<br />
48%<br />
50%<br />
52%<br />
75%<br />
Percentage of Patients for<br />
whom Drugs are Ineffective<br />
Depression<br />
Asthma<br />
CardiacArrythmias<br />
Diabetes<br />
Migraine<br />
Arthritis<br />
Osteoporosis<br />
Cancer<br />
Source: TRENDS in Molecular Medicine, 7(5), 201-204.)<br />
PHARMACOGENETICS<br />
Targeted Therapeutic Agents<br />
Afatinib<br />
Erlotinib EGFR, KRAS<br />
Gefitinib Small Molecules<br />
Cetuximab<br />
EGFR<br />
Vemurafenib<br />
Dabrafenib<br />
BRAF<br />
Trametinib<br />
Crizotinib<br />
ALK<br />
Panitumumab EGFR, KRAS<br />
Imatinib c-KIT, PDGFR<br />
Oncology Drug List<br />
Capecitabine<br />
5-fluouracil<br />
Tegafur<br />
Irinotecan<br />
Cisplatin<br />
Carboplatin<br />
Oxaliplatin<br />
Methotrexate<br />
Gemcitabine<br />
Cytarabine<br />
Cyclophosphamide<br />
Paclitaxel<br />
Docetaxel<br />
Doxorubicin/Adriamycin<br />
Pemetrex<br />
Tamoxifen<br />
Original<br />
Approval<br />
1998<br />
1999<br />
2002<br />
2003<br />
2004<br />
2006<br />
2007<br />
2011<br />
2012<br />
2013<br />
2014<br />
Selected Drugs with Specific<br />
Actionable Guidance in Labeling<br />
Drugs<br />
Biomarker<br />
Trastuzumab............... HER2<br />
Denileukin Diftitox..... CD25/IL2<br />
-<br />
-<br />
Rasburicase................. G6PD<br />
Imatinib........................ C-Kit, PDGFR, FIP1L1<br />
Cetuximab................... EGFR;<br />
KRAS<br />
-<br />
-<br />
Panitumumab............. EGFR,<br />
KRAS<br />
Lapatinib...................... HER2<br />
Nilotinib........................ Ph Chromosome<br />
-<br />
-<br />
Vemurafenib............... BRAF V600E<br />
Crizotinib..................... ALK<br />
Pertuzumab................ HER2<br />
Tafinlar/Mekinist........ BRAF V600E/ V600K<br />
Afatinib......................... EGFR Exon 19 deletions or<br />
Exon 21 (L858R) Substitutions<br />
Center for Excellence in Genetics