Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors: a retrospective, multicenter, real-world study.


Journal

ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685

Informations de publication

Date de publication:
08 2021
Historique:
received: 23 03 2021
revised: 31 05 2021
accepted: 02 07 2021
pubmed: 6 8 2021
medline: 30 10 2021
entrez: 5 8 2021
Statut: ppublish

Résumé

Despite its proven activity as third-line treatment in gastrointestinal stromal tumors (GIST), regorafenib can present a poor tolerability profile which often leads to treatment modifications and transient or permanent discontinuation; thus, in clinical practice physicians usually adopt various dosing and interval schedules to counteract regorafenib-related adverse events and avoid treatment interruption. The aim of this real-world study was to investigate the efficacy and safety of personalized schedules of regorafenib in patients with metastatic GIST, in comparison with the standard schedule (160 mg daily, 3-weeks-on, 1-week-off). Institutional registries across seven Italian reference centers were retrospectively reviewed and data of interest retrieved to identify patients with GIST who had received regorafenib from February 2013 to January 2021. The Kaplan-Meier method was used to estimate survival and the log-rank test to make comparisons. Of a total of 152 patients with GIST, 49 were treated with standard dose, while 103 received personalized schedules. At a median follow-up of 36.5 months, median progression-free survival was 5.6 months [95% confidence interval (CI) 3.73-11.0 months] versus 9.7 months (95% CI 7.9-14.5 months) in the standard-dose and the personalized schedule groups, respectively [hazard ratio (HR) 0.51; 95% CI 0.34-0.75; P = 0.00052]. Median overall survival was 16.6 months (95% CI 14.1-21.8 months) versus 20.5 months (95% CI 15.0-25.4 months), respectively (HR 0.75; 95% CI 0.49-1.22; P = 0.16). Regorafenib-personalized schedules are commonly adopted in daily clinical practice of high-volume GIST expert centers and correlate with significant improvement of therapeutic outcomes. Therefore, regorafenib treatment optimization in patients with GIST may represent the best strategy to maximize long-term therapy.

Sections du résumé

BACKGROUND
Despite its proven activity as third-line treatment in gastrointestinal stromal tumors (GIST), regorafenib can present a poor tolerability profile which often leads to treatment modifications and transient or permanent discontinuation; thus, in clinical practice physicians usually adopt various dosing and interval schedules to counteract regorafenib-related adverse events and avoid treatment interruption. The aim of this real-world study was to investigate the efficacy and safety of personalized schedules of regorafenib in patients with metastatic GIST, in comparison with the standard schedule (160 mg daily, 3-weeks-on, 1-week-off).
PATIENTS AND METHODS
Institutional registries across seven Italian reference centers were retrospectively reviewed and data of interest retrieved to identify patients with GIST who had received regorafenib from February 2013 to January 2021. The Kaplan-Meier method was used to estimate survival and the log-rank test to make comparisons.
RESULTS
Of a total of 152 patients with GIST, 49 were treated with standard dose, while 103 received personalized schedules. At a median follow-up of 36.5 months, median progression-free survival was 5.6 months [95% confidence interval (CI) 3.73-11.0 months] versus 9.7 months (95% CI 7.9-14.5 months) in the standard-dose and the personalized schedule groups, respectively [hazard ratio (HR) 0.51; 95% CI 0.34-0.75; P = 0.00052]. Median overall survival was 16.6 months (95% CI 14.1-21.8 months) versus 20.5 months (95% CI 15.0-25.4 months), respectively (HR 0.75; 95% CI 0.49-1.22; P = 0.16).
CONCLUSIONS
Regorafenib-personalized schedules are commonly adopted in daily clinical practice of high-volume GIST expert centers and correlate with significant improvement of therapeutic outcomes. Therefore, regorafenib treatment optimization in patients with GIST may represent the best strategy to maximize long-term therapy.

Identifiants

pubmed: 34352702
pii: S2059-7029(21)00183-6
doi: 10.1016/j.esmoop.2021.100222
pmc: PMC8350191
pii:
doi:

Substances chimiques

Phenylurea Compounds 0
Pyridines 0
regorafenib 24T2A1DOYB

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

100222

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure All authors have declared no competing interests.

Auteurs

M Nannini (M)

Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. Electronic address: margherita.nannini@aosp.bo.it.

A Rizzo (A)

Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

M C Nigro (MC)

Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

B Vincenzi (B)

Department of Oncology, University Campus Bio-Medico, Rome, Italy.

A Mazzocca (A)

Department of Oncology, University Campus Bio-Medico, Rome, Italy.

G Grignani (G)

Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy.

A Merlini (A)

Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy.

L D'Ambrosio (L)

Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy.

F Tolomeo (F)

Division of Medical Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy.

G Badalamenti (G)

Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.

L Incorvaia (L)

Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.

A Bonasera (A)

Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.

E Fumagalli (E)

Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

D Miliziano (D)

Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

F Ligorio (F)

Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

A Brunello (A)

Medical Oncology 1, Department of Oncology, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.

B Chiusole (B)

Medical Oncology 1, Department of Oncology, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.

S Gasperoni (S)

Translational Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy.

M Novelli (M)

Department of Statistical Sciences, University of Bologna, Bologna, Italy.

M A Pantaleo (MA)

Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi University Hospital, Bologna, Italy.

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Classifications MeSH