Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors

Area of Science:

• Oncology
• Pharmacology
• Hepatology

Background:

• Regorafenib, a multi-kinase inhibitor, is approved for metastatic colorectal cancer, hepatocellular carcinoma, and gastrointestinal stromal tumors (GIST).
• Severe hepatobiliary toxicity (HT) is documented in colorectal cancer patients on regorafenib, but not extensively studied in GIST patients.
• Real-world data on regorafenib-associated HT in GIST is limited.

Purpose of the Study:

• To determine the incidence and clinical course of regorafenib-associated hepatic toxicity (HT) in patients with metastatic GIST.
• To evaluate the impact of HT management on treatment continuation and clinical outcomes in GIST patients.
• To provide insights into real-world safety and efficacy of regorafenib in GIST.

Main Methods:

• Retrospective analysis of 21 heavily pretreated metastatic GIST patients treated with regorafenib between 2012 and 2014.
• Hepatic toxicity (HT) defined by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 serum enzyme and bilirubin alterations.
• Kaplan-Meier curves used to calculate time to clinical progression and overall survival.

Main Results:

• Severe hepatic toxicity (HT) occurred in 5 out of 21 (23.5%) heavily pretreated GIST patients.
• In 80% (4 out of 5) of cases with severe HT, regorafenib treatment was successfully continued.
• Continued regorafenib treatment, with optimized management, aimed to maximize individual treatment benefit.

Conclusions:

• Regorafenib-associated severe hepatic toxicity (HT) occurs in a significant minority of GIST patients.
• Careful clinical monitoring and proactive management strategies are essential for safe continuation of regorafenib therapy.
• Optimized management of HT enables sustained regorafenib treatment, contributing to favorable clinical outcomes in GIST.