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Efficacy and safety exposure-response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study.

التفاصيل البيبلوغرافية
العنوان: Efficacy and safety exposure-response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study.
المؤلفون: T'jollyn H; Clinical Pharmacology and Pharmacometrics, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium., Ackaert O; Clinical Pharmacology and Pharmacometrics, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium. oackaert@its.jnj.com., Chien C; Clinical Pharmacology, Hutchison MediPharma International, Florham Park, NJ, USA., Lopez-Gitlitz A; Janssen Research & Development, Los Angeles, USA., McCarthy S; Janssen Research and Development, Raritan, NJ, USA., Ruixo CP; Clinical Pharmacology and Pharmacometrics, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium., Karsh L; The Urology Center of Colorado, Denver, CO, USA., Chi K; BC Cancer and Vancouver Prostate Centre, Vancouver, Canada., Chowdhury S; Guy's, King's, and St. Thomas' Hospitals and the Sarah Cannon Research Institute, London, UK., Ruixo JP; Clinical Pharmacology and Pharmacometrics, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium., Agarwal N; Huntsman Cancer Institute, University of Utah, Salt Lake City, USA.
المصدر: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2022 May; Vol. 89 (5), pp. 629-641. Date of Electronic Publication: 2022 Apr 02.
نوع المنشور: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Springer Verlag Country of Publication: Germany NLM ID: 7806519 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0843 (Electronic) Linking ISSN: 03445704 NLM ISO Abbreviation: Cancer Chemother Pharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: Berlin : Springer Verlag
Original Publication: Berlin, New York, Springer International.
مواضيع طبية MeSH: Exanthema*/chemically induced , Prostatic Neoplasms, Castration-Resistant*, Androgen Antagonists/adverse effects ; Castration ; Humans ; Male ; Pruritus/chemically induced ; Thiohydantoins
مستخلص: Purpose: Apalutamide plus androgen-deprivation therapy (ADT) has been approved for treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) based on data from phase 3 TITAN study. This analysis was conducted to describe pharmacokinetics of apalutamide and N-desmethyl-apalutamide and explore relationships between apalutamide exposure and selected clinical efficacy and safety observations.
Methods: 1052 patients were randomized to apalutamide + ADT (n = 525) or placebo + ADT (n = 527). A previously developed population pharmacokinetic model was applied. Cox regression analysis investigated the relationships between apalutamide exposure and overall survival (OS; n = 1004) and radiographic progression-free survival (rPFS; n = 1003). Logistic regression analysis assessed the relationships between apalutamide exposure and selected clinically relevant adverse events (n = 1051).
Results: Apalutamide + ADT treatment was efficacious in extending rPFS and OS versus placebo + ADT. Within a relatively narrow apalutamide exposure range (coefficient of variation: 22%), no statistical association was detected between rPFS, OS and apalutamide exposure quartiles. Incidence of skin rash and pruritus increased significantly with increasing apalutamide exposure.
Conclusions: Differences in apalutamide exposure were not associated with clinically relevant differences in rPFS or OS in patients with mCSPC. Patients with increased apalutamide exposure are more likely to develop skin rash and pruritus. Dose reductions may improve these adverse events, based on an individual risk-benefit approach.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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فهرسة مساهمة: Keywords: Apalutamide; Exposure–response; Metastatic; Prostate cancer
المشرفين على المادة: 0 (Androgen Antagonists)
0 (Thiohydantoins)
0 (apalutamide)
تواريخ الأحداث: Date Created: 20220402 Date Completed: 20220503 Latest Revision: 20220727
رمز التحديث: 20221213
DOI: 10.1007/s00280-022-04427-1
PMID: 35366072
قاعدة البيانات: MEDLINE
الوصف
تدمد:1432-0843
DOI:10.1007/s00280-022-04427-1