Activity of axitinib in progressive advanced solitary fibrous tumour: Results from an exploratory, investigator-driven phase 2 clinical study.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
01 2019
Historique:
received: 01 10 2018
revised: 26 10 2018
accepted: 30 10 2018
pubmed: 12 12 2018
medline: 6 5 2020
entrez: 12 12 2018
Statut: ppublish

Résumé

To explore the activity of axitinib in advanced solitary fibrous tumour (SFT). In this investigator-driven phase II study on axitinib in advanced and progressive SFT, patients received axitinib, 5 mg bis in day (BID), until progression or limiting toxicity. Pathologic diagnosis was centrally reviewed, distinguishing malignant SFT (M-SFT) and high-grade/dedifferentiated SFT (HG/D-SFT) subtypes. The primary end-point was the overall response rate (ORR) by Choi criteria (Choi). Secondary end-points were response by Response Evaluation Criteria in Solid Tumours (RECIST), progression-free survival (PFS) and overall survival (OS). From April 2015 and October 2017, 17 eligible patients entered the study (metastatic: 17; SFT subtype: 13 M-SFT, 4 HG/D-SFT; prior treatment: 9 antiangiogenics, 5 cytotoxics). All patients were evaluable for response. The best Choi response was seven partial response (PR) (ORR, 41.2%), six stable disease (SD) and four progressions. Choi-ORR was 54% (7/13) when only M-SFTs were considered. Four of seven responsive patients were pretreated with pazopanib. No responses were detected in HG/D-SFT. Best RECIST response was one PR (5.9%), 14 SD and two progressions. Toxicity was as expected. Median Choi-PFS was 5.1 (interquartile range [IQR]: 2.5-14.8) months. Median Choi-PFS was 14.8 (IQR: 5.1-18.0) and 2.8 (IQR: 2.0-5.9) months for patients responsive and non-responsive by Choi, respectively (p = 0.0416). At a 14.4-month median follow-up, median OS was 25.3 months. This study showed that axitinib is active in progressive advanced SFT. One-half of patients carrying the malignant variant of the disease responded, with a >12-month median progression arrest. Responses were better detected with Choi and seen even in patients resistant to other antiangiogenics. Tolerability was good.

Sections du résumé

BACKGROUND
To explore the activity of axitinib in advanced solitary fibrous tumour (SFT).
PATIENTS AND METHODS
In this investigator-driven phase II study on axitinib in advanced and progressive SFT, patients received axitinib, 5 mg bis in day (BID), until progression or limiting toxicity. Pathologic diagnosis was centrally reviewed, distinguishing malignant SFT (M-SFT) and high-grade/dedifferentiated SFT (HG/D-SFT) subtypes. The primary end-point was the overall response rate (ORR) by Choi criteria (Choi). Secondary end-points were response by Response Evaluation Criteria in Solid Tumours (RECIST), progression-free survival (PFS) and overall survival (OS).
RESULTS
From April 2015 and October 2017, 17 eligible patients entered the study (metastatic: 17; SFT subtype: 13 M-SFT, 4 HG/D-SFT; prior treatment: 9 antiangiogenics, 5 cytotoxics). All patients were evaluable for response. The best Choi response was seven partial response (PR) (ORR, 41.2%), six stable disease (SD) and four progressions. Choi-ORR was 54% (7/13) when only M-SFTs were considered. Four of seven responsive patients were pretreated with pazopanib. No responses were detected in HG/D-SFT. Best RECIST response was one PR (5.9%), 14 SD and two progressions. Toxicity was as expected. Median Choi-PFS was 5.1 (interquartile range [IQR]: 2.5-14.8) months. Median Choi-PFS was 14.8 (IQR: 5.1-18.0) and 2.8 (IQR: 2.0-5.9) months for patients responsive and non-responsive by Choi, respectively (p = 0.0416). At a 14.4-month median follow-up, median OS was 25.3 months.
CONCLUSION
This study showed that axitinib is active in progressive advanced SFT. One-half of patients carrying the malignant variant of the disease responded, with a >12-month median progression arrest. Responses were better detected with Choi and seen even in patients resistant to other antiangiogenics. Tolerability was good.

Identifiants

pubmed: 30528807
pii: S0959-8049(18)31472-2
doi: 10.1016/j.ejca.2018.10.024
pii:
doi:

Substances chimiques

Angiogenesis Inhibitors 0
Protein Kinase Inhibitors 0
Axitinib C9LVQ0YUXG

Types de publication

Clinical Trial, Phase II Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

225-233

Informations de copyright

Copyright © 2018 Elsevier Ltd. All rights reserved.

Auteurs

S Stacchiotti (S)

Medical Oncology Unit 2, Medical Oncology Department, Fondazione IRCCS Istituto Nazione dei Tumori, Milan, Italy. Electronic address: silvia.stacchiotti@istitutotumori.mi.it.

N Simeone (N)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

S Lo Vullo (S)

Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

C Morosi (C)

Radiology Department, Fondazione IRCCS Istituto Nazione dei Tumori, Milan, Italy.

F G Greco (FG)

Radiology Department, Fondazione IRCCS Istituto Nazione dei Tumori, Milan, Italy.

A Gronchi (A)

Sarcoma Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

M Barisella (M)

Diagnostic Pathology and Laboratory Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

P Collini (P)

Diagnostic Pathology and Laboratory Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

N Zaffaroni (N)

Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

G P Dagrada (GP)

Diagnostic Pathology and Laboratory Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

A M Frezza (AM)

Medical Oncology Unit 2, Medical Oncology Department, Fondazione IRCCS Istituto Nazione dei Tumori, Milan, Italy.

L Mariani (L)

Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

P G Casali (PG)

Medical Oncology Unit 2, Medical Oncology Department, Fondazione IRCCS Istituto Nazione dei Tumori, Milan, Italy; Medical Oncology and Hemato-Oncology Department, University of Milan, Milano, Italy.

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