# Regorafenib

Source: https://onco.cc/drugs/regorafenib/  
OnCo record `regorafenib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A sorafenib successor that became the first second-line drug proven to prolong life in liver cancer (2017).

## Summary

Regorafenib is an oral multi-kinase inhibitor of VEGFR1-3, TIE2, PDGFR, FGFR, KIT, RET and RAF, a successor to sorafenib with broader targets. It is approved for previously treated metastatic colorectal cancer (CORRECT, 2012), GIST after imatinib and sunitinib (GRID, 2013) and hepatocellular carcinoma after sorafenib (2017). RESORCE showed overall survival of 10.6 versus 7.8 months versus placebo after sorafenib progression (HR 0.63), the first second-line survival benefit in liver cancer; sequencing sorafenib then regorafenib gave a median 26 months from sorafenib start. Hand-foot skin reaction (53%, 13% grade 3 or higher), hypertension and fatigue are common at 160 mg, so start-low escalation (ReDOS in colorectal cancer) is widely used. Its colorectal benefit is small, and fruquintinib now competes there. For a newcomer, it is a broad anti-angiogenic pill used late in three cancers.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-07
- Brand: Stivarga
- Modality: Small-molecule multi-kinase inhibitor
- Mechanism: Oral inhibitor of VEGFR1-3, TIE2, PDGFR, FGFR, KIT, RET and RAF.
- Approvals: US 2012: Metastatic colorectal cancer, previously treated; US 2013: GIST after imatinib and sunitinib; US 2017: HCC previously treated with sorafenib; US 2012: Metastatic colorectal cancer after fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF and, if RAS wild-type, anti-EGFR therapy; EU 2013: Metastatic colorectal cancer after available therapies; England (NICE) 2023: Metastatic colorectal cancer after previous treatment or when those treatments are unsuitable
- Dosing: Oral; 160 mg daily for 3 weeks of each 4-week cycle
- Toxicity (grade 3+): Hand-foot skin reaction 13%; Hypertension 15%; Fatigue 9%

## Notes

- In bowel cancer: CORRECT (2013) gave OS 6.4 versus 5.0 months in refractory metastatic disease, a modest benefit with significant side effects, so it is now usually placed after trifluridine/tipiracil. ReDOS (start at 80 mg and escalate weekly) improves tolerability; hepatotoxicity carries a boxed warning, with liver function checked every 2 weeks for the first 2 months.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Regorafenib
- FDA label: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/203085s013lbl.pdf
- NICE TA866: regorafenib for previously treated metastatic colorectal cancer: https://www.nice.org.uk/guidance/ta866
- EMA Stivarga: https://www.ema.europa.eu/en/medicines/human/EPAR/stivarga

## Connected records

- cancers: [Advanced hepatocellular carcinoma (BCLC C)](https://onco.cc/cancers/hcc-advanced/), [BRAF V600E-mutant colorectal cancer](https://onco.cc/cancers/braf-v600e-colorectal/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastrointestinal stromal tumour (GIST)](https://onco.cc/cancers/gist/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Imatinib-resistant GIST](https://onco.cc/cancers/gist-imatinib-resistant/), [KIT exon 11-mutant GIST](https://onco.cc/cancers/gist-kit-exon-11/), [KRAS G12C-mutant colorectal cancer](https://onco.cc/cancers/kras-g12c-colorectal/), [Osteosarcoma](https://onco.cc/cancers/osteosarcoma/), [PDGFRA D842V-mutant GIST](https://onco.cc/cancers/gist-pdgfra-d842v/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [CRAF (RAF1)](https://onco.cc/targets/raf1/), [EphA2 receptor](https://onco.cc/targets/epha2/), [KIT](https://onco.cc/targets/kit/), [RET](https://onco.cc/targets/ret/), [TIE2 receptor (TEK)](https://onco.cc/targets/tie2/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- companies: [Bayer](https://onco.cc/companies/bayer/), [Teclison](https://onco.cc/companies/teclison/)
- trials: ["Thymalfasin Immunotherapy Study with Triple Regimen in Advanced MSS/pMMR Colorectal Cancer"](https://onco.cc/trials/nct06829355/), [5-Fluorouracil/Leucovorin (5FU/LV) in Combination With Regorafenib in Patients With Metastatic Colorectal Cancer](https://onco.cc/trials/nct06887218/), [A Phase Ib/II Clinical Study of Regorafenib Combined With Toripalimab and Albumin-bound Paclitaxel for the Third-line Treatment of Advanced Pancreatic Cancer](https://onco.cc/trials/nct07040228/), [A Phase Ib/II Study of SYS6090 Combination Therapy in Advanced Colorectal Cancer](https://onco.cc/trials/nct07750041/), [A Study Comparing BL-M07D1 With Physician's Choice Therapy in Patients With HER2 IHC3+ Advanced Colorectal Cancer Who Failed Prior Treatment With Oxaliplatin, F](https://onco.cc/trials/nct07730489/), [A Study of Continued Treatment With Regorafenib in Participants With Solid Tumors Who Have Participated in Other Bayer Studies](https://onco.cc/trials/nct06246643/), [An Open-Label Study to Enable Continued Treatment Access for Subjects Previously Enrolled in Studies of Ruxolitinib](https://onco.cc/trials/nct02955940/), [Assessing a Regorafenib-irinotecan Combination Versus Regorafenib Alone in Metastatic Colorectal Cancer Patients](https://onco.cc/trials/nct03829462/), [CONCUR](https://onco.cc/trials/concur/), [CORRECT](https://onco.cc/trials/correct/), [Cryoablation Combined with Sintilimab Plus Regorafenib in Previously Treated Colorectal Cancer Liver Metastasis](https://onco.cc/trials/nct05057052/), [Efficacy And Safety Of Hydroxychloroquine Combined With Methotrexate, Capecitabine And Bevacizumab Vs. Regorafenib In Participants With Refractory Metastatic Co](https://onco.cc/trials/nct06949982/), [GBM AGILE](https://onco.cc/trials/gbm-agile/), [GRID](https://onco.cc/trials/grid/), [GSL Synthetase Inhibitor Plus Immune Checkpoint Inhibitor and/or Regorafenib in Previously Treated pMMR/MSS CRC.](https://onco.cc/trials/nct06558773/), [IMblaze370](https://onco.cc/trials/imblaze370/), [Injection of SHR-A1811 Versus Physician Choiced Treatment in Patients With Advanced Colorectal Cancer Who Had Failed to Respond to Oxaliplatin, 5-fu, ](https://onco.cc/trials/nct06199973/), [KN 046 Plus Regorafenib in MSS Metastatic Colorectal Cancer](https://onco.cc/trials/nct05985109/), [Phase IIb Study of AST-3424 in Patients With AKR1C3-high Expressing Advanced Hepatocellular Carcinoma](https://onco.cc/trials/nct07310173/), [Radiotherapy Plus Iparomlimab and Tuvonralimab (QL1706), Regorafenib, and CAPOX as Neoadjuvant Therapy for pMMR/MSS LARC.](https://onco.cc/trials/nct06911684/), [REGOBONE](https://onco.cc/trials/regobone/), [Regorafenib (Reg) and Lorigerlimab (Lor), RELO Regimen, in Treatment of High-risk Patients With Colorectal Cancer With Radiographic Occult Molecular Residual Di](https://onco.cc/trials/nct07071961/), [Regorafenib Alone or in Combination With Hypofractionated/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer](https://onco.cc/trials/nct05963490/), [Regorafenib Combined With Irinotecan Drug-Eluting Beads for Colorectal Cancer Liver Metastases](https://onco.cc/trials/nct05794971/), [Regorafenib in Combination With Multimodal Metronomic Chemotherapy for Chemo-resistant Metastatic Colorectal Cancers](https://onco.cc/trials/nct06425133/), [Regorafenib With Low-dose Chemotherapies and Aspirin Followed by Standard Chemotherapies in Metastatic Colorectal Cancer](https://onco.cc/trials/nct05462613/), [RESORCE](https://onco.cc/trials/resorce/), [Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis](https://onco.cc/trials/nct06047379/), [STREAM-2: Second-line Treatment With REgorafenib in Advanced RAS-Mutant Colorectal Cancer](https://onco.cc/trials/nct07213570/), [Study of XL092 + Atezolizumab vs Regorafenib in Participants With Metastatic Colorectal Cancer](https://onco.cc/trials/nct05425940/), [TAPUR (Targeted Agent and Profiling Utilization Registry)](https://onco.cc/trials/tapur/), [TATE and Pembrolizumab (MK3475) in mCRC and NSCLC](https://onco.cc/trials/nct04701476/), [The Purpose of This Trial is to Determine if Regorafenib Plus Durvalumab (MEDI4736) is Safe and Effective in Treatment of Chemo Refractory Advanced Biliary Tract Cancers](https://onco.cc/trials/nct04781192/), [The Study of JMT101 Combined With Irinotecan as a ≥3rd-Line Treatment in Metastatic Colorectal Cancer](https://onco.cc/trials/nct07134205/)
- key papers: [Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370)](https://onco.cc/key-papers/paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019/), [CodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancer](https://onco.cc/key-papers/paper-codebreak-300-nejm-2023/), [GRID: regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib](https://onco.cc/key-papers/paper-grid-regorafenib-gist-lancet-2013/), [Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT)](https://onco.cc/key-papers/paper-grothey-correct-regorafenib-lancet-2013/), [The threat of medical misinformation: a case of ivermectin toxicity in a pediatric oncology patient](https://onco.cc/key-papers/paper-gilene-ivermectin-toxicity-paediatric-oncology-2025/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)
- terms: [Anti-VEGF class toxicities (hypertension, proteinuria, bleeding, perforation)](https://onco.cc/terms/antiangiogenic-toxicities/), [Colorectal cancer drugs in England: what NICE has recommended](https://onco.cc/terms/colorectal-uk-drug-access/), [Hand-foot syndrome and hand-foot skin reaction](https://onco.cc/terms/hand-foot-syndrome/)
- pathways: [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Hepatocellular carcinoma (KEGG map)](https://onco.cc/pathways/hepatocellular-carcinoma-signalling/), [The angiogenic switch & tumour vessels](https://onco.cc/pathways/angiogenic-switch/)

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