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Individualized Dosing Patterns in the Treatment of Older Patients with Gastrointestinal Stromal Tumors: Results of a Registry-Based Observational National Cohort Study Including 871 Patients.
Bleckman, Roos F; Broekman, K Esther; Roets, Evelyne; Mohammadi, Mohammed; Desar, Ingrid M E; Gelderblom, Hans; Mathijssen, Ron H J; Steeghs, Neeltje; de Graeff, Pauline; Reyners, Anna K L.
Afiliación
  • Bleckman RF; University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. r.f.bleckman@umcg.nl.
  • Broekman KE; Department of Medical Oncology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. r.f.bleckman@umcg.nl.
  • Roets E; University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Mohammadi M; Department of Medical Oncology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
  • Desar IME; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Gelderblom H; Leiden University Medical Center, Leiden, The Netherlands.
  • Mathijssen RHJ; Radboud University Medical Center, Nijmegen, The Netherlands.
  • Steeghs N; Leiden University Medical Center, Leiden, The Netherlands.
  • de Graeff P; Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
  • Reyners AKL; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Drugs Aging ; 41(2): 165-176, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38123766
ABSTRACT

BACKGROUND:

While the effectiveness of tyrosine kinase inhibitors (TKIs) seems similar in older patients with gastrointestinal stromal tumors (GIST) compared with younger patients, toxicities in older patients treated with TKIs more often lead to discontinuation of treatment.

OBJECTIVE:

To better understand the age-related pharmacology and pharmacodynamic differences in patients with GIST treated with TKIs, the primary aim of this study was to evaluate TKI dosing patterns in older patients with GIST, while the secondary aims were to evaluate differences in imatinib trough plasma concentrations between age groups and to compare the overall survival (OS) in patients with and without dose reductions in all treatment lines in a palliative setting.

METHODS:

Patients (18 years of age or older) with histologically proven GIST diagnosed between January 2009 and June 2021 and treated with one or more lines of TKIs were selected from the Dutch GIST Registry (DGR) database. Age groups were divided into younger patients (age <70 years) and older patients (age ≥70 years). All imatinib trough plasma concentrations of blood withdrawals taken from initiation of imatinib until a maximum of 1 year of treatment with imatinib were collected. Reasons for first adjustment of treatment were classified as adverse event, dose modification, progressive disease and other reasons. The next treatment steps after first adjustment of treatment were defined as dose escalation, dose reduction, dose interruption, or end of treatment. The association of dose reduction and OS was analyzed using the landmark approach.

RESULTS:

Overall, 871 patients were included in this study, including 577 younger patients and 294 older patients. Older patients more often had an adverse event as the reason for first adjustment of treatment with both imatinib (45.6%; p < 0.001) and sunitinib (58.6%; p = 0.224) compared with younger patients (19.5% and 42.7%, respectively). Adjustment of imatinib and sunitinib after starting on a standard dose because of an adverse event most often resulted in dose reduction in both age groups. Median trough plasma concentrations of all samples taken within the first year after initiation of imatinib were higher in older patients (1228 ng/mL, interquartile range [IQR] 959-1687) compared with younger patients (1035 ng/mL [IQR 773-1377]; p < 0.001). No significant differences were seen between OS in patients with or without dose reduction in all treatment lines (imatinib p = 0.270; sunitinib p = 0.547; and regorafenib p = 0.784).

CONCLUSION:

Older patients showed higher imatinib trough plasma concentrations compared with younger patients and also had earlier and more often adverse events as the reason for first adjustment of treatment with imatinib followed by dose reduction. However, in a landmark analysis, patients with imatinib dose reductions had no poorer outcomes compared with patients not requiring a dose reduction.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tumores del Estroma Gastrointestinal / Neoplasias Gastrointestinales / Antineoplásicos Límite: Adolescent / Adult / Aged / Humans Idioma: En Revista: Drugs Aging Asunto de la revista: GERIATRIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Nueva Zelanda

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tumores del Estroma Gastrointestinal / Neoplasias Gastrointestinales / Antineoplásicos Límite: Adolescent / Adult / Aged / Humans Idioma: En Revista: Drugs Aging Asunto de la revista: GERIATRIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Nueva Zelanda