Stivarga: Uses, Dosage & Side Effects
An oral multikinase inhibitor for the treatment of metastatic colorectal cancer, gastrointestinal stromal tumors (GIST), and hepatocellular carcinoma (liver cancer)
Stivarga (regorafenib) is an oral multikinase inhibitor used in the treatment of three advanced cancers in adults: metastatic colorectal cancer, gastrointestinal stromal tumors (GIST), and hepatocellular carcinoma (liver cancer). Regorafenib works by simultaneously blocking multiple protein kinases involved in tumor growth, blood vessel formation (angiogenesis), and the tumor microenvironment. It is prescribed when previous standard treatments have failed or are no longer effective. Stivarga is taken as a daily tablet in a cyclic schedule of 3 weeks on and 1 week off, and requires a prescription and careful medical monitoring throughout treatment.
Quick Facts: Stivarga
Key Takeaways
- Stivarga (regorafenib) is an oral multikinase inhibitor that blocks multiple protein kinases involved in tumor growth, angiogenesis, and the tumor microenvironment, used when other cancer treatments have failed.
- It is approved for three indications: metastatic colorectal cancer (after prior fluoropyrimidine, anti-VEGF, and anti-EGFR therapy), gastrointestinal stromal tumors (after imatinib and sunitinib), and hepatocellular carcinoma (after sorafenib).
- The standard dose is 160 mg (four 40 mg tablets) taken once daily after a low-fat meal for 3 weeks, followed by 1 week off treatment; liver function must be monitored before and during treatment due to the risk of severe hepatotoxicity.
- Common side effects include hand-foot skin reaction, fatigue, diarrhea, hypertension, and liver enzyme elevations; serious side effects include liver failure, gastrointestinal perforation, and severe bleeding.
- Both women and men must use effective contraception during treatment and for at least 8 weeks after the last dose; avoid grapefruit juice and strong CYP3A4 inhibitors or inducers during treatment.
What Is Stivarga and What Is It Used For?
Stivarga contains the active substance regorafenib, a small-molecule multikinase inhibitor that targets a broad range of protein kinases. Protein kinases are enzymes that play critical roles in signaling pathways within cells, regulating processes such as cell growth, division, survival, and blood vessel formation. In cancer, many of these pathways become abnormally active, driving uncontrolled tumor growth and the development of new blood vessels that feed the tumor (a process called angiogenesis). By inhibiting multiple kinases simultaneously, regorafenib disrupts several of these cancer-promoting processes at once.
Specifically, regorafenib targets kinases involved in three key aspects of cancer biology. First, it blocks angiogenic receptors including VEGFR1, VEGFR2, VEGFR3, and TIE2, which are critical for the formation of new blood vessels that supply nutrients and oxygen to growing tumors. Second, it inhibits oncogenic kinases such as KIT, RET, RAF1, BRAF, and BRAFV600E, which directly drive tumor cell proliferation and survival. Third, it targets stromal and immune-related kinases including PDGFR, FGFR, and CSF1R, which shape the tumor microenvironment and influence the interaction between tumor cells and surrounding immune and stromal cells. This multi-targeted mechanism sets regorafenib apart from single-target therapies and provides broad-spectrum antitumor activity.
Regorafenib is structurally related to sorafenib, another multikinase inhibitor, but has a distinct pharmacological profile with additional target kinases. Both drugs share activity against VEGFR and RAF kinases, but regorafenib demonstrates more potent inhibition of several targets including TIE2 and certain mutant forms of BRAF. Clinical studies have confirmed the efficacy of regorafenib even in patients whose disease has progressed on sorafenib, supporting its role as a distinct therapeutic agent.
Stivarga is approved by the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and regulatory authorities in numerous other countries for the following indications:
- Metastatic colorectal cancer (mCRC): Stivarga is used in adult patients whose cancer has spread to other parts of the body and who have already received or cannot receive treatment with fluoropyrimidine-based chemotherapy, an anti-VEGF therapy (such as bevacizumab), and an anti-EGFR therapy (such as cetuximab or panitumumab, if the tumor is RAS wild-type). The landmark CORRECT trial demonstrated that regorafenib significantly improved overall survival compared with placebo in this heavily pre-treated patient population, with a hazard ratio of 0.77.
- Gastrointestinal stromal tumors (GIST): Stivarga is used in adult patients with GIST that has spread to other parts of the body or that cannot be removed surgically, after prior treatment with imatinib and sunitinib (the standard first- and second-line treatments for advanced GIST). The GRID trial showed that regorafenib significantly improved progression-free survival in this setting, establishing it as the standard third-line treatment for advanced GIST.
- Hepatocellular carcinoma (HCC): Stivarga is used in adult patients with liver cancer who have previously been treated with sorafenib. The RESORCE trial demonstrated that regorafenib significantly improved overall survival compared with placebo in patients who had tolerated and then progressed on sorafenib, with a hazard ratio of 0.63. This made regorafenib the first second-line treatment to show a survival benefit in advanced HCC.
Colorectal cancer is one of the most common cancers worldwide, and a significant proportion of patients eventually develop metastatic disease that requires systemic therapy. GIST is a relatively uncommon cancer of the gastrointestinal tract, characterized by mutations in KIT or PDGFRA that drive tumor growth. Hepatocellular carcinoma is the most common form of primary liver cancer, often arising in the context of chronic liver disease such as cirrhosis from hepatitis B or C infection, alcohol use, or metabolic liver disease. For all three indications, Stivarga provides a treatment option when standard earlier-line therapies have been exhausted.
Unlike therapies that block a single molecular target, Stivarga inhibits a wide spectrum of kinases simultaneously. This multi-targeted approach allows it to attack cancer from several angles: cutting off the tumor blood supply, directly suppressing cancer cell growth, and modifying the tumor microenvironment. While this broad activity contributes to its efficacy, it also explains the range of side effects that require careful medical monitoring.
What Should You Know Before Taking Stivarga?
Contraindications
There are specific situations in which Stivarga must not be used. Understanding these contraindications is essential for safe treatment.
- Hypersensitivity: Do not take Stivarga if you are allergic to regorafenib or any of the other ingredients in the product (listed in the contents section below). Signs of an allergic reaction may include widespread rash, nausea, fever, shortness of breath, jaundice, or changes in liver chemistry.
- Severe hepatic impairment: Stivarga should not be used in patients with severely impaired liver function (Child-Pugh C), as there is insufficient data on its use in this population and the drug carries a significant risk of hepatotoxicity.
Warnings and Precautions
Fatal liver injury has been reported with Stivarga. Your doctor will perform liver function tests before starting treatment and at least every two weeks during the first two months. Seek immediate medical attention if you develop yellowing of the skin or eyes (jaundice), dark urine, confusion, or disorientation. These may be signs of serious liver damage.
Before and during treatment with Stivarga, discuss the following with your doctor:
- Liver problems: If you have pre-existing liver disease, including Gilbert’s syndrome (characterized by intermittent jaundice), you may be at higher risk for liver complications. Liver function tests will be performed regularly, and your dose may need to be reduced or treatment stopped if significant liver damage occurs.
- Infections: Stivarga may increase your risk of infections. Report symptoms such as high fever, severe cough with or without increased mucus, severe sore throat, shortness of breath, burning sensation or pain during urination, unusual vaginal discharge, or redness, swelling, or pain anywhere on the body. Your doctor may temporarily stop treatment.
- Bleeding: If you have or have had bleeding problems, or if you take blood thinners such as warfarin or phenprocoumon, inform your doctor. Stivarga can increase the risk of bleeding. This includes severe bleeding in the gastrointestinal tract (stomach, throat, rectum, or bowel), lungs, kidneys, mouth, vagina, and/or brain. Seek immediate medical attention if you notice blood in your stool (or black stool), blood in urine, stomach pain, or if you cough up or vomit blood.
- Gastrointestinal perforation or fistula: Stivarga may cause holes in the wall of the gastrointestinal tract (perforation) or abnormal connections between organs (fistula). Seek immediate medical help if you develop severe abdominal pain that does not go away, bloody vomit, or red or black stool.
- Heart problems: If you have chest pain or heart problems, your doctor will monitor your heart function before and during treatment. Seek immediate medical attention if you experience chest discomfort or pain radiating to the shoulders, arms, back, neck, or jaw; shortness of breath; sudden sweating with cold, clammy skin; or dizziness or faintness. These may be signs of a heart attack or reduced blood flow to the heart.
- Posterior reversible encephalopathy syndrome (PRES): Contact your doctor immediately if you develop severe or persistent headache, visual disturbances, seizures, lack of energy, drowsiness, reduced consciousness, or changes in mental status such as confusion, memory loss, or disorientation.
- Hypertension (high blood pressure): Stivarga can raise blood pressure. Your doctor will monitor your blood pressure before and during treatment and may prescribe medication to control it if needed.
- Aneurysms and artery dissections: If you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in a blood vessel wall, inform your doctor.
- Thrombotic microangiopathy (TMA): Tell your doctor if you develop fever, fatigue, bruising, bleeding, swelling, confusion, vision loss, or seizures. These may indicate damage to the smallest blood vessels.
- Surgery and wound healing: Stivarga may impair wound healing. If you have recently undergone or are about to undergo surgery, treatment may need to be paused until the wound has healed.
- Skin problems (hand-foot skin reaction): Stivarga commonly causes redness, pain, swelling, or blistering on the palms and soles of the feet. If you notice skin changes, contact your doctor. Protective creams, shoe insoles, and gloves may help manage symptoms. Your doctor may adjust the dose or stop treatment if the condition worsens.
Pregnancy and Breastfeeding
Stivarga should not be used during pregnancy unless absolutely necessary, as it may cause harm to the developing baby. Tell your doctor if you are pregnant, think you may be pregnant, or are planning to become pregnant. Your doctor will discuss the potential risks of taking Stivarga during pregnancy.
Both women and men of reproductive potential must use effective contraception during treatment and for at least 8 weeks after the last dose of Stivarga. This is essential because the drug may harm the unborn child.
Breastfeeding must be stopped during treatment with Stivarga, as the drug may affect the growth and development of the nursing infant. Discuss with your doctor if you are breastfeeding or planning to breastfeed.
Stivarga may reduce fertility in both men and women. Talk to your doctor about fertility preservation options before starting treatment.
Driving and Operating Machinery
It is not known whether Stivarga directly affects the ability to drive or operate machinery. However, do not drive or use machines if you experience any treatment-related symptoms that affect your concentration or reaction time, such as fatigue, dizziness, or visual disturbances.
Important Information About Ingredients
Stivarga contains 56.06 mg of sodium (the main component of table salt) per daily dose of 4 tablets. This corresponds to approximately 3% of the WHO-recommended maximum daily dietary sodium intake for adults. If you are on a sodium-restricted diet, take this into consideration.
Stivarga also contains 1.68 mg of lecithin (derived from soya) per daily dose. If you have a soy allergy, inform your doctor before starting treatment.
How Does Stivarga Interact with Other Drugs?
Regorafenib is primarily metabolized by the CYP3A4 and UGT1A9 enzyme systems. Medications that inhibit or induce these enzymes can significantly alter the levels of regorafenib and its active metabolites in the body, potentially affecting both efficacy and safety. Additionally, regorafenib itself can affect the metabolism and blood levels of other drugs. It is essential to inform your doctor about all medications, supplements, and herbal products you are taking.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Ketoconazole, itraconazole, posaconazole, voriconazole (strong CYP3A4 inhibitors) | Increased regorafenib exposure, greater risk of toxicity | Avoid combination; may significantly increase side effects |
| Rifampicin and other strong CYP3A4 inducers | Decreased regorafenib and active metabolite levels | Avoid combination; may reduce efficacy of Stivarga |
| Phenytoin, carbamazepine, phenobarbital (antiepileptics) | CYP3A4 induction; decreased regorafenib levels | Avoid combination; consider alternative antiepileptics |
| St. John’s wort (herbal supplement) | Strong CYP3A4 induction; significantly reduced regorafenib levels | Must not be taken during Stivarga treatment |
| Warfarin, phenprocoumon (anticoagulants) | Increased bleeding risk; possible changes in INR | Monitor INR frequently; increased risk of hemorrhage |
Minor Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Rosuvastatin, fluvastatin, atorvastatin (statins) | Regorafenib inhibits BCRP and OATP1B1 transporters; increased statin levels | Monitor for statin-related side effects (muscle pain, liver issues) |
| Methotrexate | Regorafenib may increase methotrexate exposure via BCRP inhibition | Monitor for methotrexate toxicity; dose adjustment may be needed |
| Mefenamic acid, diflunisal, niflumic acid (UGT1A9 inhibitors) | May alter levels of regorafenib metabolites | Use with caution; monitor for increased side effects |
| Clarithromycin, telithromycin (antibiotics) | Moderate CYP3A4 inhibition; possible increase in regorafenib exposure | Use with caution; consider alternative antibiotics if available |
| Grapefruit juice | CYP3A4 inhibition; may increase regorafenib levels | Must be avoided during Stivarga treatment |
Always inform your doctor about all medications you are taking, including prescription and over-the-counter drugs, vitamins, nutritional supplements, and herbal products. Some interactions may require dose adjustments, more frequent monitoring, or switching to alternative medications.
What Is the Correct Dosage of Stivarga?
Stivarga should always be taken exactly as your doctor has instructed. If you are unsure about anything regarding your dose, consult your doctor or pharmacist. The dose may be adjusted during treatment based on how you respond and whether you experience side effects.
Adults
Standard Dosing – All Indications
Dose: 160 mg (four 40 mg tablets) once daily
Schedule: Take for 3 weeks (21 days) followed by 1 week (7 days) off treatment = one 28-day cycle
How to take: Swallow the tablets whole with water after a low-fat meal (containing less than 30% fat). Take at the same time each day.
Example low-fat meal: 1 portion of cereal (about 30 g), 1 glass of skimmed milk, 1 slice of toast with jam, 1 glass of apple juice, and 1 cup of coffee or tea (approximately 520 calories, 2 g fat).
Duration: Continue treatment for as long as you benefit and do not experience unacceptable side effects, as determined by your doctor.
Dose Adjustments
Your doctor may need to reduce your dose or temporarily stop treatment if you experience significant side effects. Dose reductions typically follow this pattern:
- First dose reduction: 120 mg daily (three 40 mg tablets)
- Second dose reduction: 80 mg daily (two 40 mg tablets)
- If further reduction is needed: Your doctor may decide to permanently discontinue Stivarga
If you have mild hepatic impairment, no dose adjustment is necessary. If you have mild or moderate hepatic impairment that develops during treatment, your doctor will monitor you closely. Stivarga should not be used if you have severe hepatic impairment (Child-Pugh C), as there is insufficient safety data in this population.
No dose adjustment is necessary for mild, moderate, or severe renal impairment.
Children
Stivarga is not recommended for use in children and adolescents under 18 years of age. There is no relevant use for the approved indications in the pediatric population (colorectal cancer, GIST, and hepatocellular carcinoma), and safety and efficacy data in children are not available.
Elderly
No specific dose adjustment is recommended based on age alone. However, elderly patients may be more susceptible to certain side effects, and your doctor will monitor you carefully throughout treatment.
Missed Dose
If you miss a dose, take it on the same day as soon as you remember. Do not take two doses on the same day to make up for a missed dose from the previous day. Inform your doctor that you missed a dose.
Overdose
Contact your doctor immediately if you have taken more than the prescribed dose. An overdose may increase the likelihood or severity of certain side effects, particularly skin reactions (rash, blisters, redness, pain, swelling, itching, or peeling), voice changes (dysphonia), frequent or loose stools (diarrhea), mouth sores, dry mouth, decreased appetite, hypertension, and excessive tiredness.
Always take Stivarga after a low-fat meal. Taking it on an empty stomach or after a high-fat meal can significantly alter the amount of drug absorbed into your body. Do not drink grapefruit juice during treatment, as it may interfere with how Stivarga works. If you vomit after taking your dose, do not take extra tablets; instead, inform your doctor.
What Are the Side Effects of Stivarga?
Like all medicines, Stivarga can cause side effects, although not everyone experiences them. Some side effects can be serious and potentially life-threatening. Your doctor will perform regular blood tests and clinical assessments to monitor for these complications. It is important to report any new or worsening symptoms promptly.
Serious Side Effects Requiring Immediate Medical Attention
Treatment with Stivarga carries a risk of serious liver damage, including liver failure with fatal outcomes. Seek immediate medical attention if you notice yellowing of the skin or whites of the eyes, dark-colored urine, or confusion and disorientation.
Stivarga can cause serious bleeding in the gastrointestinal tract, lungs, kidneys, mouth, vagina, and/or brain. Seek immediate medical attention if you notice blood in your stool or black stool, blood in your urine, stomach pain, or if you cough up or vomit blood.
Seek immediate medical help if you develop severe abdominal pain that does not go away, bloody vomit, or red or black stool. These may indicate a hole in the wall of the gastrointestinal tract.
Side Effects by Frequency
Very Common
May affect more than 1 in 10 people
- Decreased platelet count (thrombocytopenia) – may cause easy bruising or bleeding
- Decreased red blood cell count (anemia)
- Decreased appetite and reduced food intake
- High blood pressure (hypertension)
- Voice changes or hoarseness (dysphonia)
- Frequent or loose stools (diarrhea)
- Mouth pain or dry mouth, tongue pain, mouth sores (stomatitis/mucositis)
- Nausea
- Vomiting
- Elevated bilirubin levels (hyperbilirubinemia)
- Elevated liver enzymes (increased transaminases)
- Hand-foot skin reaction: redness, pain, blisters, and swelling on palms and soles
- Rash
- Weakness (asthenia) and excessive tiredness (fatigue)
- Pain (including abdominal and back pain)
- Constipation
- Fever
- Weight loss
Common
May affect up to 1 in 10 people
- Decreased white blood cell count (leukopenia)
- Decreased thyroid function (hypothyroidism)
- Low levels of potassium, phosphate, calcium, sodium, or magnesium in the blood
- Elevated uric acid levels (hyperuricemia)
- Dehydration
- Headache
- Tremor
- Peripheral neuropathy (numbness, tingling, weakness, or pain)
- Taste disturbances
- Dry mouth
- Heartburn (gastroesophageal reflux)
- Stomach or intestinal infection (gastroenteritis)
- Hair loss (alopecia)
- Dry skin
- Skin peeling (exfoliative rash)
- Sudden involuntary muscle contractions (muscle spasms)
- Protein in urine (proteinuria)
- Elevated digestive enzyme levels (increased amylase and lipase)
- Abnormal blood clotting (abnormal INR values)
Uncommon
May affect up to 1 in 100 people
- Signs/symptoms of allergic reaction (hypersensitivity) – widespread rash, nausea, fever, shortness of breath, jaundice
- Heart attack, chest pain (myocardial infarction and ischemia)
- Severe rise in blood pressure causing headache, confusion, blurred vision, nausea, vomiting, and seizures (hypertensive crisis)
- Inflammation of the pancreas (pancreatitis) – abdominal pain, nausea, vomiting, fever
- Nail disorders (grooves, splitting, or changes to nails)
- Multiple skin rashes (erythema multiforme)
Rare
May affect up to 1 in 1,000 people
- Blood clots in small blood vessels (thrombotic microangiopathy, TMA)
- Certain types of skin cancer (keratoacanthoma/squamous cell carcinoma)
- Headache, confusion, seizures, and vision loss with or without high blood pressure (posterior reversible encephalopathy syndrome/PRES)
- Severe skin and/or mucous membrane reactions with painful blisters, fever, and extensive skin peeling (Stevens-Johnson syndrome and toxic epidermal necrolysis)
Not Known
Frequency cannot be estimated from available data
- Enlargement and weakening of a blood vessel wall, or a tear in a blood vessel wall (aneurysms and arterial dissections)
- Lack of energy, confusion, drowsiness, tremors, reduced consciousness – may be signs of brain toxicity caused by high ammonia levels in the blood (hyperammonemic encephalopathy)
If you experience any side effects, including those not listed here, tell your doctor or pharmacist. You can also report suspected side effects to your national pharmacovigilance authority (e.g., the EMA in Europe, the FDA MedWatch program in the United States, or the MHRA Yellow Card Scheme in the United Kingdom) to help monitor the ongoing benefit-risk profile of Stivarga.
How Should You Store Stivarga?
Proper storage of Stivarga is essential to maintain the effectiveness and safety of the medication. Follow these storage guidelines:
- Keep in original packaging: Store the tablets in the original bottle to protect from moisture. Keep the desiccant (the small moisture-absorbing packet) inside the bottle.
- Close tightly: Always close the bottle cap tightly after each use.
- After opening: Once the bottle has been opened, the tablets must be discarded after 7 weeks, even if there are remaining tablets. Mark the date you first opened the bottle.
- Expiry date: Do not use after the expiry date stated on the carton and bottle label (after EXP). The expiry date refers to the last day of that month.
- Children: Keep this medicine out of the sight and reach of children.
- Disposal: Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. These measures help protect the environment.
What Does Stivarga Contain?
Active Substance
The active substance is regorafenib. Each film-coated tablet contains 40 mg of regorafenib. The standard daily dose of 4 tablets delivers 160 mg of regorafenib.
Inactive Ingredients (Excipients)
- Tablet core: Microcrystalline cellulose, croscarmellose sodium, magnesium stearate, povidone (K-25), colloidal anhydrous silica
- Film coating: Iron oxide red (E172), iron oxide yellow (E172), lecithin (derived from soya), macrogol 3350, polyvinyl alcohol (partially hydrolyzed), talc, titanium dioxide (E171)
Appearance and Pack Sizes
Stivarga 40 mg tablets are light pink, oval-shaped, and imprinted with “BAYER” on one side and “40” on the other side. Each bottle contains 28 film-coated tablets. Stivarga is available in packs containing 1 bottle or 3 bottles. Not all pack sizes may be available in every country.
The desiccant (a small container of moisture-absorbing material) must remain inside the bottle to protect the tablets from moisture. Do not swallow the desiccant.
Marketing Authorization Holder and Manufacturer
Stivarga is manufactured and marketed by Bayer AG, Kaiser-Wilhelm-Allee, 51368 Leverkusen, Germany. For more information about this medicine, contact the local representative of the marketing authorization holder in your country.
Frequently Asked Questions About Stivarga
Stivarga (regorafenib) is used to treat three types of advanced cancer in adults: metastatic colorectal cancer that has progressed after standard treatments, gastrointestinal stromal tumors (GIST) that have progressed after treatment with imatinib and sunitinib, and hepatocellular carcinoma (liver cancer) that has been previously treated with sorafenib. In all three indications, Stivarga is used when earlier treatment lines have failed.
Take 4 tablets (160 mg total) once daily at the same time each day, after a low-fat meal containing less than 30% fat. Swallow the tablets whole with water. Follow a schedule of 3 weeks on treatment followed by 1 week off. Do not drink grapefruit juice during treatment. If you vomit after taking your dose, do not take extra tablets. Continue treatment as long as your doctor advises.
Hand-foot skin reaction (palmar-plantar erythrodysesthesia) is one of the most common side effects of Stivarga, causing redness, pain, swelling, or blistering on the palms of your hands and soles of your feet. If you experience these symptoms, contact your doctor. Preventive measures include using moisturizing creams, wearing comfortable shoes with padded insoles, and avoiding hot water. Your doctor may recommend reducing the dose or temporarily stopping treatment until symptoms improve.
Yes, severe and potentially fatal liver damage (hepatotoxicity) has been reported with Stivarga. This is one of the most serious risks of treatment. Your doctor will test your liver function before starting treatment and regularly during treatment (at least every two weeks during the first two months). Warning signs include yellowing of the skin and eyes, dark urine, confusion, and abdominal pain. If you notice any of these symptoms, seek immediate medical attention. Patients with severe liver impairment should not take Stivarga.
Grapefruit juice contains compounds that inhibit the CYP3A4 enzyme, which is involved in the metabolism of regorafenib. Drinking grapefruit juice while taking Stivarga can increase the levels of the drug in your blood, potentially leading to more severe side effects. For the same reason, other strong CYP3A4 inhibitors should also be avoided. Stick to water, tea, coffee, or other non-grapefruit beverages during treatment.
In the pivotal CORRECT trial, Stivarga significantly improved overall survival in patients with metastatic colorectal cancer who had progressed on all standard therapies. The median overall survival was 6.4 months with regorafenib versus 5.0 months with placebo, representing a 23% reduction in the risk of death (HR 0.77). While the absolute improvement may appear modest, it is clinically meaningful in this heavily pre-treated population with limited treatment options. The CONCUR trial in an Asian population showed even greater benefit, with a hazard ratio of 0.55.
References
- European Medicines Agency (EMA). Stivarga (regorafenib) – Summary of Product Characteristics. Last updated 2025. Available from: EMA EPAR.
- U.S. Food and Drug Administration (FDA). Stivarga (regorafenib) Prescribing Information. Revised 2024. Available from: FDA Drug Label.
- Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303–312. doi:10.1016/S0140-6736(12)61900-X.
- Demetri GD, Reichardt P, Kang YK, et al. 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 trial. Lancet. 2013;381(9863):295–302. doi:10.1016/S0140-6736(12)61857-1.
- Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56–66. doi:10.1016/S0140-6736(16)32453-9.
- Li J, Qin S, Xu R, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(6):619–629. doi:10.1016/S1470-2045(15)70156-7.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 1.2025.
- Cervantes A, Adam R, Rosmorduc O, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(1):10–32.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023.
- Bekaii-Saab TS, Ou FS, Ahn DH, et al. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(8):1070–1082. doi:10.1016/S1470-2045(19)30272-4.
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in oncology, gastroenterology, hepatology, and clinical pharmacology.
Medical Content
iMedic Oncology Editorial Team – specialist physicians in gastrointestinal oncology and hepatology with clinical experience in targeted cancer therapy
Medical Review
iMedic Medical Review Board – independent panel verifying accuracy against EMA SmPC, FDA label, NCCN, and ESMO guidelines
Pharmacology Review
iMedic Clinical Pharmacology Team – specialists in drug interactions, pharmacokinetics, and medication safety
Accessibility & SEO
iMedic Digital Health Team – ensuring WCAG 2.2 AAA compliance and optimal search visibility
All content follows the GRADE evidence framework and is reviewed according to international medical guidelines. iMedic receives no commercial funding from pharmaceutical companies.