Regorafenib: Application and progress of multi-target kinase inhibitors in tumor treatment

Regorafenib is an oral multi-target kinase inhibitor mainly used for the second-line or third-line treatment of advanced colorectal cancer, gastrointestinal stromal tumors and hepatocellular carcinoma. This article will start from four aspects: drug mechanism, clinical application, efficacy data and manufacturer, focusing on analyzing its targeting characteristics and clinical research results, and mainly introducing indications and adverse reaction management. Structurally, it is divided into five parts: overview, mechanism details, clinical research, practical application and summary to help readers systematically understand the drug.

Drug mechanism of action and target characteristics

Regorafenib achieves anti-tumor effects by inhibiting angiogenesis-related receptors such as VEGFR1-3, PDGFR, and FGFR, while blocking multiple tumor signaling pathways such as RAF, KIT, and RET. Its unique feature is that it can simultaneously affect the tumor microenvironment and the tumor cells themselves. This "dual-pathway" mechanism enables it to demonstrate efficacy against a variety of advanced solid tumors. Drug metabolism is mainly through the CYP3A4 enzyme, indicating the need to pay attention to interactions with other drugs. Preclinical studies have shown that regorafenib can significantly inhibit tumor angiogenesis and metastasis formation, which lays a theoretical foundation for its subsequent clinical development.

Key clinical studies and efficacy data

In the CORRECT study, regorafenib extended the median overall survival of patients with metastatic colorectal cancer to 6.4 months, a significant improvement compared with the placebo group. The RESORCE trial confirmed that among patients with hepatocellular carcinoma who failed sorafenib treatment, the median survival time in the regorafenib group reached 10.6 months. The following are some key data:

Clinical application and adverse reaction management

The standard dose of regorafenib is 160 mg/day, and the drug is taken for 3 weeks and then stopped for 1 week. Common adverse reactions include hand-foot skin reactions (about 50%), hypertension (30%) and fatigue, most of which can be controlled through dose adjustment and supportive treatment. Special attention should be paid to liver function monitoring during clinical use, and it is contraindicated in patients with Child-Pugh class C. In recent years, researchers are exploring its combination with immune checkpoint inhibitors. Preliminary data show that it may improve the immune response in the tumor microenvironment, but more evidence is needed to support it.

Summary and Outlook

As a multi-target tyrosine kinase inhibitor, regorafenib provides a new treatment option for patients with a variety of advanced tumors. Its clear survival benefit has been recommended by international guidelines, but individualized medication and adverse reaction management are still clinical priorities. In the future, with the deepening of research on combination therapy, the role of this drug in comprehensive tumor treatment may be further enhanced. The original drug is currently produced by Bayer, with the trade name Stivarga, and generic drugs have been approved in China.

Quote sources:
1. "New England Journal of Medicine": CORRECT study data (2013)
2. Center for Drug Evaluation of the National Medical Products Administration: Regorafenib Instructions
3. Bayer’s official product information: Stivarga® Product Manual
4. Chinese Society of Clinical Oncology (CSCO) Colorectal Cancer Diagnosis and Treatment Guidelines 2023 Edition