Efficacy and safety of regorafenib in patients with metastatic or locally advanced chondrosarcoma: Results of a non-comparative, randomised, double-blind, placebo controlled, multicentre phase II study.
Metastatic chondrosarcoma
Progression after standard chemotherapy
Regorafenib
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:
06 2021
06 2021
Historique:
received:
23
02
2021
revised:
12
03
2021
accepted:
21
03
2021
pubmed:
26
4
2021
medline:
26
10
2021
entrez:
25
4
2021
Statut:
ppublish
Résumé
This multi-cohort trial explored the efficacy and safety of regorafenib for patients with advanced sarcomas of bone origin; this report details the cohort of patients with metastatic or locally advanced chondrosarcoma (CS), progressing after prior chemotherapy. Patients with CS, progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progressive disease. The primary endpoint was progression-free rate (PFR) at 12 weeks. With one-sided α of 0.05, and 80% power, at least 16/24 progression-free patients at 12 weeks were needed for success (P0 = 50%, P1 = 75%). From September 2014 to February 2019, 46 patients were included in the CS cohort, and 40 patients were evaluable for efficacy: 16 on placebo and 24 on regorafenib. Thirteen patients (54.2%; 95% CI [35.8%-[) were non-progressive at 12 weeks on regorafenib versus 5 (31.3%; 95% CI [13.2%-[);) on placebo. Median PFS was 19.9 weeks on regorafenib, and 8.0 on placebo. Fourteen placebo patients crossed over to regorafenib after progression. The most common grade ≥3 treatment-related adverse events on regorafenib included hypertension (12%), asthenia (8%), thrombocytopenia (8%) and diarrhoea (8%). One episode of fatal liver dysfunction occurred on regorafenib. Although the primary endpoint was not met statistically in this small randomised cohort, there is modest evidence to suggest that regorafenib might slow disease progression in patients with metastatic CS after the failure of prior chemotherapy. The trial is registered at ClinicalTrials.gov (NCT02389244).
Sections du résumé
BACKGROUND
This multi-cohort trial explored the efficacy and safety of regorafenib for patients with advanced sarcomas of bone origin; this report details the cohort of patients with metastatic or locally advanced chondrosarcoma (CS), progressing after prior chemotherapy.
PATIENTS AND METHODS
Patients with CS, progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progressive disease. The primary endpoint was progression-free rate (PFR) at 12 weeks. With one-sided α of 0.05, and 80% power, at least 16/24 progression-free patients at 12 weeks were needed for success (P0 = 50%, P1 = 75%).
RESULTS
From September 2014 to February 2019, 46 patients were included in the CS cohort, and 40 patients were evaluable for efficacy: 16 on placebo and 24 on regorafenib. Thirteen patients (54.2%; 95% CI [35.8%-[) were non-progressive at 12 weeks on regorafenib versus 5 (31.3%; 95% CI [13.2%-[);) on placebo. Median PFS was 19.9 weeks on regorafenib, and 8.0 on placebo. Fourteen placebo patients crossed over to regorafenib after progression. The most common grade ≥3 treatment-related adverse events on regorafenib included hypertension (12%), asthenia (8%), thrombocytopenia (8%) and diarrhoea (8%). One episode of fatal liver dysfunction occurred on regorafenib.
CONCLUSION
Although the primary endpoint was not met statistically in this small randomised cohort, there is modest evidence to suggest that regorafenib might slow disease progression in patients with metastatic CS after the failure of prior chemotherapy.
CLINICAL TRIAL REGISTRATION
The trial is registered at ClinicalTrials.gov (NCT02389244).
Identifiants
pubmed: 33895682
pii: S0959-8049(21)00206-9
doi: 10.1016/j.ejca.2021.03.039
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Phenylurea Compounds
0
Pyridines
0
regorafenib
24T2A1DOYB
Banques de données
ClinicalTrials.gov
['NCT02389244']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108-118Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement FD received travel grants from Pharmamar, and Leo Pharma attended advisory boards for Bayer, Lilly. CC attended advisory boards for Leo Pharma, OM attended advisory boards and chaired meetings with Amgen, Astra Zeneca, Bayer, Bleuprint, Eli Lilly, Roche, Servier, PBR received travel grants form Pfizer, Takeda, JYB receives research support and honoraria from Eisei, Eli Lilly, MSD, BMS, GSK, Ignyta, Novartis, Pharmamar and Roche unrelated to this work, and AI, CP, NP, OC, LC, CD, MC, LM, MR, EB, SC, FB, CS, SPN, CB, VV, AH, ESB, have declared no conflicts of interest.