Intra-individual Dose Escalation of Abiraterone According to Its Plasma Exposure in Patients with Progressive Metastatic Castration-Resistant Prostate Cancer: Results of the OPTIMABI Trial.


Journal

Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849

Informations de publication

Date de publication:
04 Jul 2024
Historique:
accepted: 13 06 2024
medline: 4 7 2024
pubmed: 4 7 2024
entrez: 4 7 2024
Statut: aheadofprint

Résumé

Trough abiraterone concentration (ABI C This multicentre, non-randomised study consisted of two sequential steps. In step 1, all patients started treatment with 1000 mg of AA once daily. Abiraterone C In the intention-to-treat analysis (ITT), 81 patients were included in step 1. In all, 21 (26%) patients were underexposed in step 1, and 8 of them (38%) experienced tumour progression within the first 6 months. A total of 71 patients (88%) completed the Girerd self-reported questionnaire. Of the patients, 62% had a score of 0, and 38% had a score of 1 or 2 (minimal compliance failure), without a significant difference in mean ABI C The ITT and per-protocol analyses showed no statistical association between ABI underexposure and an increased risk of early tumour progression in patients with mCRPC, while the Bayesian estimator showed an association. However, other strategies than dose escalation at the time of progression need to be evaluated. Treatment adherence appeared to be uniformly good in the present study. Finally, the use of a Bayesian approach to recover samples collected outside the predefined blood collection time window could benefit the conduct of clinical trials based on drug monitoring. OPTIMABI trial is registered as National Clinical Trial number NCT03458247, with the EudraCT number 2017-000560-15).

Sections du résumé

BACKGROUND AND OBJECTIVE OBJECTIVE
Trough abiraterone concentration (ABI C
METHODS METHODS
This multicentre, non-randomised study consisted of two sequential steps. In step 1, all patients started treatment with 1000 mg of AA once daily. Abiraterone C
RESULTS RESULTS
In the intention-to-treat analysis (ITT), 81 patients were included in step 1. In all, 21 (26%) patients were underexposed in step 1, and 8 of them (38%) experienced tumour progression within the first 6 months. A total of 71 patients (88%) completed the Girerd self-reported questionnaire. Of the patients, 62% had a score of 0, and 38% had a score of 1 or 2 (minimal compliance failure), without a significant difference in mean ABI C
CONCLUSION CONCLUSIONS
The ITT and per-protocol analyses showed no statistical association between ABI underexposure and an increased risk of early tumour progression in patients with mCRPC, while the Bayesian estimator showed an association. However, other strategies than dose escalation at the time of progression need to be evaluated. Treatment adherence appeared to be uniformly good in the present study. Finally, the use of a Bayesian approach to recover samples collected outside the predefined blood collection time window could benefit the conduct of clinical trials based on drug monitoring. OPTIMABI trial is registered as National Clinical Trial number NCT03458247, with the EudraCT number 2017-000560-15).

Identifiants

pubmed: 38963459
doi: 10.1007/s40262-024-01396-x
pii: 10.1007/s40262-024-01396-x
doi:

Banques de données

ClinicalTrials.gov
['NCT03458247']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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Auteurs

Jérôme Alexandre (J)

Medical Oncology Department, Université Paris Cité, Institut du Cancer Paris CARPEM, AP-HP, Hôpital Cochin-Port Royal, 75014, Paris, France.

Stephane Oudard (S)

Medical Oncology Department, Université Paris Cité, Institut du Cancer Paris CARPEM, AP-HP, Hôpital Européen George Pompidou, 75015, Paris, France.

Lisa Golmard (L)

Department of Genetics, Institut Curie, 75005, Paris, France.
Université Paris Sciences and Lettres, Paris, France.

Luca Campedel (L)

Department of Medical Oncology, AP-HP, Hôpital Pitié-Salpêtrière, 75013, Paris, France.

Mourad Mseddi (M)

Biologie du Médicament-Toxicologie, Institut du Cancer Paris CARPEM, AP-HP, Hôpital Cochin, 75014, Paris, France.

Sylvain Ladoire (S)

Department of Medical Oncology, Centre Georges François Leclerc, 21000, Dijon, France.

Ahmed Khalil (A)

Department of Medical Oncology, AP-HP, Hopital Tenon, 75020, Paris, France.

Denis Maillet (D)

Department of Medical Oncology, Université de Lyon, Hôpital Lyon-Sud, 69495, Pierre-Bénite, France.
Faculté de médecine Jacques Lisfranc, 42270, Saint Etienne, France.

Christophe Tournigand (C)

Department of Medical Oncology, AP-HP, Hôpital Henri Mondor, 94000, Créteil, France.

Blaise Pasquiers (B)

Biologie du Médicament-Toxicologie, Institut du Cancer Paris CARPEM, AP-HP, Hôpital Cochin, 75014, Paris, France.

Françoise Goirand (F)

Hôpital Universitaire Dijon Bourgogne, Laboratoire de Pharmacologie-Toxicologie, 21000, Dijon, France.

Joseph Berthier (J)

Hôpital Universitaire Dijon Bourgogne, Laboratoire de Pharmacologie-Toxicologie, 21000, Dijon, France.

Jérôme Guitton (J)

Hôpital Lyon-Sud, Hospices Civils de Lyon, Biochemistry and Pharmacology-Toxicology Laboratory, 69495, Pierre Benite, France.

Charles Dariane (C)

Department of Urology, Université Paris Cité, Inserm UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants-Malades (INEM), AP-HP, Hôpital européen Georges-Pompidou, 75015, Paris, France.

Florence Joly (F)

Department of Medical Oncology, Centre François Baclesse, University Unicaen, 14000, Caen, France.

Evanguelos Xylinas (E)

Department of Urology, Université de Paris Cité, AP-HP, Hôpital Bichat-Claude Bernard, 75018, Paris, France.

Jean Louis Golmard (JL)

Retired Academic Statistician, Paris, France.

Hendy Abdoul (H)

Université Paris Cité, AP-HP, URC Paris Centre, 75014, Paris, France.

Alicja Puszkiel (A)

Université Paris Cité, Inserm UMR-S1144, Paris, France.
Institut de Cancérologie et de Radiothérapie Brétilien, Oncologie, 35760, Saint-Grégoire, France.

Xavier Decleves (X)

Université Paris Cité, Inserm UMR-S1144, Paris, France.

Edith Carton (E)

Institut de Cancérologie et de Radiothérapie Brétilien, Oncologie, 35760, Saint-Grégoire, France.

Audrey Thomas (A)

Université de Paris Cité; CNRS, INSERM, CiTCoM, U1268, 75006, Paris, France.
Institut du Cancer Paris CARPEM, AP-HP, Service de Pharmacie Clinique, Hôpital Cochin, 75014, Paris, France.

Michel Vidal (M)

Biologie du Médicament-Toxicologie, Institut du Cancer Paris CARPEM, AP-HP, Hôpital Cochin, 75014, Paris, France.
Université de Paris Cité; CNRS, INSERM, CiTCoM, U1268, 75006, Paris, France.

Olivier Huillard (O)

Medical Oncology Department, Université Paris Cité, Institut du Cancer Paris CARPEM, AP-HP, Hôpital Cochin-Port Royal, 75014, Paris, France.

Benoit Blanchet (B)

Biologie du Médicament-Toxicologie, Institut du Cancer Paris CARPEM, AP-HP, Hôpital Cochin, 75014, Paris, France. benoit.blanchet@aphp.fr.
Université de Paris Cité; CNRS, INSERM, CiTCoM, U1268, 75006, Paris, France. benoit.blanchet@aphp.fr.

Classifications MeSH