Regorafenib

(Stivarga®)

Regorafenib

Drug updated on 12/11/2024

Dosage FormTablet (oral; 40 mg)
Drug ClassKinase inhibitors
Ongoing and
Completed Studies
ClinicalTrials.gov

Indication

  • Indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an antiVEGF therapy, and, if RAS wild-type, an anti-EGFR therapy
  • Indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate
  • Hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

Latest News

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Summary
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  • This summary is based on the review of 24 systematic review(s)/meta-analysis(es). [1-24]
  • In Hepatocellular Carcinoma (HCC), Nivolumab demonstrated statistically insignificantly longer overall survival (OS), time to progression (TTP), and progression-free survival (PFS) compared to Regorafenib; however, Nivolumab had a higher overall response rate (ORR) with mixed disease control rate (DCR) results. Regorafenib combined with PD-1 inhibitors significantly improved OS (hazard ratio (HR), 0.61) and PFS (HR, 0.51) compared to monotherapy.
  • For Metastatic Colorectal Cancer (mCRC), TAS-102 plus Bevacizumab was the most effective regimen in terms of median overall survival (mOS) and median progression-free survival (mPFS), outperforming standard and dose-escalated Regorafenib treatments.
  • In Gastrointestinal Stromal Tumors (GIST), Regorafenib showed improved survival rates after the failure of Imatinib and Sunitinib, with acceptable safety profiles; it also resulted in better PFS compared to placebo, Imatinib, and Sunitinib, although Ripretinib and Masitinib exhibited superior OS.
  • Combination therapies, specifically Nivolumab plus Ipilimumab, yielded significantly higher ORR and longer OS compared to Regorafenib, Cabozantinib, and Nivolumab monotherapy.
  • Nivolumab exhibited fewer side effects and improved tolerance compared to Regorafenib in patients with HCC. However, Regorafenib combined with programmed death-1 inhibitors (R-P) resulted in a higher incidence of adverse events, including hypothyroidism, thrombocytopenia, and rash, relative to Regorafenib monotherapy.
  • In mCRC, Fruquintinib was linked to a significantly higher risk of serious adverse events compared to TAS-102 and Regorafenib, highlighting differing safety profiles among these treatments.
  • Adverse events associated with Regorafenib in GIST were predominantly mild to moderate; however, monitoring for grade 4 or higher adverse events is necessary, as Regorafenib was found to have the highest rates of high-grade adverse events compared to Ripretinib and Masitinib, which had lower rates of severe events.
  • Regorafenib demonstrates significant superiority in OS for patients with low-level alpha-fetoprotein (AFP) in HCC, while no statistical differences were observed in patients with elevated AFP; in mCRC, the studies included primarily middle-aged to elderly individuals with a slight male predominance, mostly Caucasian, and TAS-102 plus Bevacizumab ranked highest across various subgroups including age, gender, and ECOG performance status.

Product Monograph / Prescribing Information

Document TitleYearSource
Stivarga (regorafenib) Prescribing Information.2020Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ

Systematic Reviews / Meta-Analyses

Document TitleYearSource
Regorafenib plus programmed death‑1 inhibitors vs. regorafenib monotherapy in second‑line treatment for advanced hepatocellular carcinoma: A systematic review and meta‑analysis2024Oncology Letters
Impact of Systemic Treatments on Outcomes and Quality of Life in Patients with RAS-Positive Stage IV Colorectal Cancer: A Systematic Review2024Diseases (Basel, Switzerland)
Selective Internal Radiation Therapy Using Y-90 Resin Microspheres for Metastatic Colorectal Cancer: An Updated Systematic Review and Network Meta-Analysis2024Advances in Therapy
An Efficacy and Safety Comparison of Regorafenib and Nivolumab in Unresectable Hepatocellular Cancer Patients: A Systematic Review2024Acta Medica Academica
Comparison of the efficacy and safety of third-line treatments for metastatic colorectal cancer: a systematic review and network meta-analysis2023Frontiers in Oncology
Evaluation of and Current Trends in the Management of Gastrointestinal Stromal Tumors: A Systematic Review2022Cureus
Health-Related Quality of Life and Side Effects in Gastrointestinal Stromal Tumor (GIST) Patients Treated with Tyrosine Kinase Inhibitors: A Systematic Review of the Literature2022Cancers
The prognostic role of neutrophil-to-lymphocyte ratio and C-reactive protein in metastatic colorectal cancer using regorafenib: a systematic review and meta-analysis2022Journal of Gastrointestinal Oncology
The Role of Regorafenib in the Management of Advanced Gastrointestinal Stromal Tumors: A Systematic Review2022Cureus
Comparative efficacy and safety for second-line treatment with ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma progressed on sorafenib treatment: A network meta-analysis2021Medicine
Immune-Checkpoint Inhibitors for Metastatic Colorectal Cancer: A Systematic Review of Clinical Outcomes2021Cancers
Network meta-analysis of nivolumab plus ipilimumab in the second-line setting for advanced hepatocellular carcinoma2021Journal of Comparative Effectiveness Research
The integration of immune checkpoint inhibitors with VEGF targeted agents in advanced gastric and gastroesophageal adenocarcinoma: a review on the rationale and results of early phase trials2021Journal of Hematology & Oncology
Comparative Efficacy and Safety of Different Regimens of Advanced Gastrointestinal Stromal Tumors After Failure Prior Tyrosine Kinase Inhibitors: A Network Meta-Analysis2021Advances in Therapy
Optimizing Survival and the Changing Landscape of Targeted Therapy for Intermediate and Advanced Hepatocellular Carcinoma: A Systematic Review2021Journal of the National Cancer institute
Regorafenib, TAS-102, or fruquintinib for metastatic colorectal cancer: any difference in randomized trials?2020International Journal of Colorectal Disease
Incidence and risk of proteinuria associated with newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: an up-to-date meta-analysis of randomized controlled trials2020Expert Review of Clinical Pharmacology
Systematic review and network meta-analyses of third-line treatments for metastatic colorectal cancer2020Journal of Cancer Research and Clinical Oncology
Efficacy and safety of regorafenib as beyond second-line therapy in patients with metastatic colorectal cancer: an adjusted indirect meta-analysis and systematic review2020Therapeutic Advances in Medical Oncology
Systematic Review and Meta-Analysis of Multitargeted Tyrosine Kinase Inhibitors in Patients With Intractable Metastatic Colorectal Cancer2020Technology in Cancer Research & Treatment
Systemic Therapy and Sequencing Options in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-analysis2020JAMA Oncology
A systematic review and network meta-analysis of second-line therapy in hepatocellular carcinoma2020Current Oncology
Comparison of Regorafenib, Fruquintinib, and TAS-102 in Previously Treated Patients with Metastatic Colorectal Cancer: A Systematic Review and Network Meta-Analysis of Five Clinical Trials2019Medical Science Monitor
Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis2019Cancers

Clinical Practice Guidelines