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Pharmacokinetics, Safety, and Efficacy of Trastuzumab Deruxtecan with Concomitant Ritonavir or Itraconazole in Patients with HER2-Expressing Advanced Solid Tumors
DC Field | Value | Language |
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dc.contributor.author | Takahashi, Shunji | - |
dc.contributor.author | Karayama, Masato | - |
dc.contributor.author | Takahashi, Masato | - |
dc.contributor.author | Watanabe, Junichiro | - |
dc.contributor.author | Minami, Hironobu | - |
dc.contributor.author | Yamamoto, Noboru | - |
dc.contributor.author | Kinoshita, Ichiro | - |
dc.contributor.author | Lin, Chia-Chi | - |
dc.contributor.author | Im, Young-Hyuck | - |
dc.contributor.author | Achiwa, Issei | - |
dc.contributor.author | Kamiyama, Emi | - |
dc.contributor.author | Okuda, Yasuyuki | - |
dc.contributor.author | Lee, Caleb | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.date.accessioned | 2022-04-26T05:34:49Z | - |
dc.date.available | 2022-04-26T05:34:49Z | - |
dc.date.created | 2021-11-29 | - |
dc.date.created | 2021-11-29 | - |
dc.date.issued | 2021-11-01 | - |
dc.identifier.citation | Clinical Cancer Research, Vol.27 No.21, pp.5771-5780 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.other | 148851 | - |
dc.identifier.uri | https://hdl.handle.net/10371/179200 | - |
dc.description.abstract | Purpose: To evaluate drug-drug interactions between the human epidermal growth factor receptor 2 (HER2)-targeted anti-body-drug conjugate trastuzumab deruxtecan (T-DXd; DS-8201a) and the OATP1B/CYP3A inhibitor ritonavir or the strong CYP3A inhibitor itraconazole. Patients and Methods: Patients with HER2-expressing advanced solid tumors were enrolled in this phase I, open-label, single-sequence crossover study (NCT03383692) and received i.v. T-DXd 5.4 mg/kg every 3 weeks. Patients received ritonavir (cohort 1) or itraconazole (cohort 2) from day 17 of cycle 2 through the end of cycle 3. Primary endpoints were maximum serum concentration (C-max) and partial area under the concentration-time curve from beginning of cycle through day 17 (AUC(17d)) for T-DXd and deruxtecan (DXd) with (cycle 3) and without (cycle 2) ritonavir or itraconazole treatment. Results: Forty patients were enrolled (cohort 1, n = 17; cohort 2, n = 23). T-DXd C-max was similar whether combined with ritonavir [cohort 1, cycle 3/cycle 2; 90% confidence interval (CI): 1.05 (0.98-1.13)] or itraconazole [cohort 2, 1.03 (0.96-1.09)]. T-DXd AUC(17d) increased from cycle 2 to 3; however, the cycle 3/cycle 2 ratio upper CI bound remained at <= 1.25 for both cohorts. For DXd (cycle 3/cycle 2), C-max ratio was 0.99 (90% CI, 0.85-1.14) for cohort 1 and 1.04 (0.92-1.18) for cohort 2; AUC(17d) 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. | - |
dc.language | 영어 | - |
dc.publisher | American Association for Cancer Research | - |
dc.title | Pharmacokinetics, Safety, and Efficacy of Trastuzumab Deruxtecan with Concomitant Ritonavir or Itraconazole in Patients with HER2-Expressing Advanced Solid Tumors | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 방영주 | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-21-1560 | - |
dc.citation.journaltitle | Clinical Cancer Research | - |
dc.identifier.wosid | 000714656500008 | - |
dc.identifier.scopusid | 2-s2.0-85119055457 | - |
dc.citation.endpage | 5780 | - |
dc.citation.number | 21 | - |
dc.citation.startpage | 5771 | - |
dc.citation.volume | 27 | - |
dc.identifier.sci | 000714656500008 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Bang, Yung-Jue | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ANION TRANSPORTING POLYPEPTIDES | - |
dc.subject.keywordPlus | PROTEASE INHIBITORS | - |
dc.subject.keywordPlus | DRUG | - |
dc.subject.keywordPlus | BREAST | - |
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