A retrospective study of drug response indicator test (DRIT) as a predictive test for therapeutic treatment outcomes of advanced breast cancer patients (ABC)

Autor: W Rogers, Paul O. P. Ts'o, D. A. Vanecho, KR Tkaczuk, Nancy Tait, Ming Tan, E Shan, Olga B. Ioffe, SF Deamond, Stephen A. Lesko, JR Daniel, Lum Zp
Rok vydání: 2009
Předmět:
Zdroj: Cancer Research. 69:6075
ISSN: 1538-7445
0008-5472
DOI: 10.1158/0008-5472.sabcs-6075
Popis: Abstract #6075 We conducted a retrospective study of DRIT, an investigational diagnostic test to predict chemotherapy and endocrine therapy treatment outcomes in ABC. DRIT is a quantitative measurement of Drug Response Indicator (DRI) expression levels in formalin fixed, paraffin embedded tumor tissue. DRI chosen for each drug is related to the perceived mechanism of action of the drug. The quantitative measurement of DRI expression in the tumor tissue is based on the fluorescent dye-labeled monoclonal antibody (mAb) staining, followed by acquisition of digital images using computer-assisted microscopy, calibrated to an external standard. DRI expression measurement results in classification of the tumor as sensitive or resistant to a particular drug based on our in vitro studies of drug sensitivity/resistance in cell lines. If a tumor is classified as sensitive to a drug/s by DRIT, this predicts that the patient (Pt) will respond to treatment, while if a tumor is classified as resistant this predicts that the Pt will not respond to the drug/s therapy. Clinically the treatment outcome is classified into a responsive group (non-progressive disease,CR, PR, SD) & a non-responsive group (progressive disease, PD). The drugs & DRI tested are: capcitabine/thymidylate synthase; Taxanes /β-tubulin isoform III, trastuzamab/HER-2, Endocrine therapy/estrogen receptor, gemcitabine/ribonucleotide reductase. 51 ABC received mono or doublet therapy as first 3 lines of therapy-(80 treatments). The percent accuracy (number of accurate predictions/number of treatment interventions) for monotherapy is 87% (61/70), 100% (10/10) for doublet therapy and 89% (71/80) for all treatments. The accuracy of prediction for responsive patients is 86% (60/69) and 100% (11/11) for non responsive patients. DRIT diagnostic performance for 80 treatment outcome predictions for endocrine therapy and mono and doublet chemotherapy is as follows: sensitivity 1.00, specificity 0.55, positive predictive value 0.87, negative predictive value 1.00, and overall accuracy 0.88. For the standard of care outcomes, the favorable response rate for the 80 treatments is 75% (60/80), the potential favorable response rate with DRIT input is 86% (60/69) with 11 ineffective treatments identified by DRIT accurately 100% (11/11). Thus, DRIT input can identify effective (86%) & ineffective (100%) treatments in this cohort of ABC patients. DRIT is under developement as a diagnostic test to predict treatment outcomes prior to the selection of a particular drug for anticancer therapy, so that the most effective drug can be prescribed for an individual cancer patient. This retrospective study in ABC patients shows that DRIT has a potential to be a useful test to predict treatment outcomes. Supported in part by Maryland Industry Partnership Program – MIPS. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6075.
Databáze: OpenAIRE
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