Pharmacokinetics, safety, and efficacy of trastuzumab deruxtecan with concomitant ritonavir or itraconazole in patients with HER2-expressing advanced solid tumors
Journal
Clinical Cancer Research
Journal Volume
27
Journal Issue
21
Pages
5771-5780
Date Issued
2021
Author(s)
Takahashi S.
Karayama M.
Takahashi M.
Watanabe J.
Minami H.
Yamamoto N.
Kinoshita I.
Im Y.-H.
Achiwa I.
Kamiyama E.
Okuda Y.
Lee C.
Bang Y.-J.
Abstract
PURPOSE: To evaluate drug-drug interactions between the human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd; DS-8201a) and the OATP1B/CYP3A inhibitor ritonavir or the strong CYP3A inhibitor itraconazole. PATIENTS AND METHODS: ) for T-DXd and deruxtecan (DXd) with (cycle 3) and without (cycle 2) ritonavir or itraconazole treatment. RESULTS: ratio was 1.22 (1.08-1.37) and 1.18 (1.11-1.25), respectively. The safety profile of T-DXd plus ritonavir or itraconazole was consistent with previous studies of T-DXd monotherapy. T-DXd demonstrated promising antitumor activity across HER2-expressing solid-tumor types. CONCLUSIONS: T-DXd was safely combined with ritonavir or itraconazole without clinically meaningful impact on T-DXd or DXd pharmacokinetics.
SDGs
Publisher
American Association for Cancer Research Inc.
Type
journal article