Implementation of model-informed precision dosing for tamoxifen therapy in patients with breast cancer: A prospective intervention study
Abstract
Tamoxifen is an estrogen-receptor (ER) antagonist, used as adjuvant treatment of ER-positive breast cancer. It is converted by CYP2D6 into endoxifen, its most active metabolite. Patients with endoxifen plasma concentrations <16 nM face a higher risk of recurrence. The use of a priori model-informed precision dosing (MIPD) may lead to faster target attainment and thus potentially improve patient outcomes. In total, 106 evaluable patients were prospectively included in this single-arm MIPD-intervention study. Patients received a model-predicted tamoxifen dose when starting tamoxifen-treatment (65.1 % of patients received 20 mg, 16.0 % received 30 mg and 18.9 % received 40 mg). Seventy-five percent of the 40 mg group was predicted to be unable to reach the threshold of 16 nM despite receiving the highest registered dose. After attaining steady-state, 84.0 % of patients reached endoxifen levels ≥16 nM, which was not significantly higher compared to a historical control cohort (77.9 %, p = 0.17). The model showed adequate performance and correctly identified patients requiring 40 mg tamoxifen. Endoxifen samples that were acquired 4-6 weeks after treatment initiation, are informative of steady-state endoxifen levels and can be used to inform MIPD and adjust tamoxifen dosing prior to steady-state attainment. In this first MIPD implementation study for patients treated with tamoxifen, MIPD did lead to more patients achieving endoxifen levels ≥16 nM as compared to the…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 106 participants or records.
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