Toxicity management of regorafenib in patients with gastro-intestinal stromal tumour (GIST) in a tertiary cancer centre
Open Access
- 4 January 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Clinical Sarcoma Research
- Vol. 10 (1), 1-8
- https://doi.org/10.1186/s13569-019-0123-4
Abstract
Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients require dose reductions. This study aimed to evaluate regorafenib toxicities and their management in a real-world GIST population. Retrospective review of a prospectively maintained database identified 50 patients with GIST treated with regorafenib at our centre between March 2013 and September 2018. Median progression free survival (PFS) was 7.7 months [interquartile range (IQR) 2.8–14.4 months]. Median overall survival (OS) from start of regorafenib to death or last follow up was 15.7 months (IQR 9.2–28.4 months). Baseline median Eastern Cooperative Oncology Group (ECOG) performance status on starting regorafenib was 1. The main reason for discontinuing regorafenib was progressive disease (PD) (31/50 [62%]) rather than toxicity (10/50 [20%]). Grade 3–4 adverse events (AEs) were seen in 23/50 (46%) patients; palmar-plantar erythrodysesthesia (PPE) was most frequently seen (9/50 (18%)). Two patients died whilst on treatment with regorafenib from multi-organ failure secondary to sepsis (4%). Dose reductions were required in 19/50 patients (38%) and 8/50 (16%) patients started regorafenib at a lower dose band than the recommended dose (160 mg) due to comorbidities or concern over a higher individual risk of toxicity. Although PD was the main reason for discontinuing treatment, toxicity management and dosing of regorafenib remains critical. Median duration of treatment was longer compared to previous studies suggesting a durable clinical benefit with regorafenib with rigorous toxicity management.Keywords
This publication has 24 references indexed in Scilit:
- Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trialThe Lancet, 2013
- A Phase I Dose–Escalation Study of Regorafenib (BAY 73–4506), an Inhibitor of Oncogenic, Angiogenic, and Stromal Kinases, in Patients with Advanced Solid TumorsClinical Cancer Research, 2012
- One vs Three Years of Adjuvant Imatinib for Operable Gastrointestinal Stromal TumorJAMA, 2012
- Phase III study of nilotinib versus best supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinibAnnals of Oncology, 2012
- Regorafenib (BAY 73‐4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activityInternational Journal of Cancer, 2010
- Comparison of Two Doses of Imatinib for the Treatment of Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Meta-Analysis of 1,640 PatientsJournal of Clinical Oncology, 2010
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- Correlation of Computed Tomography and Positron Emission Tomography in Patients With Metastatic Gastrointestinal Stromal Tumor Treated at a Single Institution With Imatinib Mesylate: Proposal of New Computed Tomography Response CriteriaJournal of Clinical Oncology, 2007
- Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trialThe Lancet, 2006
- Efficacy and Safety of Imatinib Mesylate in Advanced Gastrointestinal Stromal TumorsThe New England Journal of Medicine, 2002