The clinical relevance of tamoxifen pharmacogenetics and therapeutic drug monitoring has been challenged, according to findings from an observational study.
“The objective of the prospective CYPTAM study was to associate endoxifen concentrations and CYP2D6 genotypes with clinical outcome[s] in patients with early-stage breast cancer receiving tamoxifen,” wrote Anabel Sanchez-Spitman, PharmD, of the Leiden University Medical Center, the Netherlands, and her colleagues in the Journal of Clinical Oncology.
“Although, in a retrospective study, an endoxifen threshold of 5.9 ng/mL for efficacy [has been] described, confirmation based on prospective studies is lacking,” they wrote.
The researchers followed 667 patients with early-stage breast malignancy who were treated with 20 mg of oral tamoxifen daily.
Dr. Sanchez-Spitman and her colleagues performed CYP2D6 genotype testing and measured blood levels of endoxifen, an active metabolite of tamoxifen, in study participants. Both of these measures were linked with relapse-free survival via statistical analysis.
After analysis, no significant association was found between endoxifen concentrations (P = .691) or CYP2D6 genotyping (P = .799) and relapse-free survival. These data were the same in both univariable and multivariable regression analysis.
“Neither categorizing endoxifen concentrations into quartiles nor using 5.9 ng/mL as threshold altered these results,” they wrote.
The authors acknowledged that a key limitation of the study was the absence of tamoxifen adherence testing, but the availability of persistence data was well collected, lessening this drawback.
“Our data do not justify therapeutic drug monitoring based on endoxifen concentrations in patients with breast cancer receiving tamoxifen,” they concluded.
The study was supported by grant funding provided by ZOLEON. The authors reported no conflicts of interest.
SOURCE: Sanchez-Spitman A et al. J Clin Oncol. 2019 Jan 24. doi: 10.1200/JCO.18.00307.