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2018 ASCO Annual Meeting!


Session: Breast Cancer—Local/Regional/Adjuvant

Type: Poster Session

Time: Saturday June 2, 8:00 AM to 11:30 AM

Location: Hall A

A prospective study on the effect of endoxifen concentration and CYP2D6 phenotypes on clinical outcome in early stage breast cancer patients receiving adjuvant tamoxifen.

Sub-category:
Adjuvant Therapy

Category:
Breast Cancer—Local/Regional/Adjuvant

Meeting:
2018 ASCO Annual Meeting

Abstract No:
523

Poster Board Number:
Poster Session (Board #15)

Citation:
J Clin Oncol 36, 2018 (suppl; abstr 523)

Author(s): Anabel Beatriz Sanchez-Spitman, Vincent O. Dezentjé, Jesse J Swen, Dirk Jan A.R. Moes, Erdogan Batman, Carolien H. Smorenburg, Lynn Jongen, Maartje Los, Patrick Neven, Hans Gelderblom, Henk-jan Guchelaar; Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, Netherlands; Department of Medical Oncology, Antoni van Leeuwenhoek, Amsterdam, Netherlands; Leiden University Medical Center, Department of Clinical Pharmacy and Toxicology, Leiden, Netherlands; Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, NL; Diaconessenhuis, Leiden, Netherlands; Antoni van Leeuwenhoek, Amsterdam, Netherlands; KU Leuven, Leuven, Belgium; St. Antonius Hospital, Nieuwegein, Netherlands; University Hospitals Leuven, Leuven, Belgium; Leiden University Medical Center, Leiden, Netherlands

Abstract Disclosures

Abstract:

Background: It has been postulated that endoxifen levels are better predictors of tamoxifen efficacy than CYP2D6 phenotype. Although in a retrospective study an endoxifen threshold of 5.9 ng/ml for efficacy was described, confirmation based on prospective studies is lacking. The objective of the prospective CYPTAM study (NTR1509) is to associate endoxifen levels and, CYP2D6 phenotypes with clinical outcome in early stage breast cancer patients receiving tamoxifen. Methods: Breast cancer patients who were receiving adjuvant tamoxifen were included. Blood samples were used for CYP2D6 genotyping and endoxifen levels by Amplichip and high-performance liquid chromatography-tandem mass spectrometry assay, respectively. Endoxifen levels and CYP2D6 phenotypes were associated with relapse-free survival (RFS) by using Cox-regression analysis. Patients who changed to an aromatase inhibitor, were censored at the time of switch. Results: A total of 667 pre and post-menopausal patients were enrolled. No association was found between endoxifen serum levels used as a continuous variable and RFS (Adjusted Harzard Ratio (HR): 0.991, 95 % CI: 0.946-1.038, p-value: 0.691). Categorizing endoxifen levels in quartiles, or using 5.9 ng/ml as threshold did not alter these results. In addition, no association was observed between CYP2D6 phenotypes and RFS(Adjusted HR: 0.929, 95 % CI 0.525-1.642, p-value 0.799). Conclusions: This first prospective clinical study shows no association between endoxifen levels and CYP2D6 phenotypes with RFS in early breast cancer patients using adjuvant tamoxifen. These results do not support the use of therapeutic drug monitoring based on endoxifen levels or CYP2D6 genotyping. Associations between Endoxifen levels and CYP2D6 phenotypes with RFS. Clinical trial information: NTR1509.


Multivariable analysis
HR95 % CIp
Endoxifen0.9910.946-10380.691
Threshold (ng/ml):
< 5.91.000Reference
> 5.91.5380.719-3.2900.267
Quartiles (ng/ml):
Q1 ( < 6.6)1.000Reference
Q2 (6,6-10,3)1.9860.909-4.3400.085
Q3 (10,3-14,1)1.3310.580-3.0590.500
Q4 ( > 14.1)0.9500.399-2.2620.907
CYP2D6 phenotypes
UM/EM1.00Reference
hetEM/IM/PM0.9290.525-1.6420.799

 
Other Abstracts in this Sub-Category:

 

1. TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score.

Meeting: 2018 ASCO Annual Meeting Abstract No: LBA1 First Author: Joseph A. Sparano
Category: Breast Cancer—Local/Regional/Adjuvant - Adjuvant Therapy

 

2. Adjuvant denosumab in early breast cancer: Disease-free survival analysis of 3,425 postmenopausal patients in the ABCSG-18 trial.

Meeting: 2018 ASCO Annual Meeting Abstract No: 500 First Author: Michael Gnant
Category: Breast Cancer—Local/Regional/Adjuvant - Adjuvant Therapy

 

3. Adjuvant denosumab in early breast cancer: First results from the international multicenter randomized phase III placebo controlled D-CARE study.

Meeting: 2018 ASCO Annual Meeting Abstract No: 501 First Author: Robert E. Coleman
Category: Breast Cancer—Local/Regional/Adjuvant - Adjuvant Therapy

 

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