Oncology Overview: Regorafenib For Metastatic Colorectal Cancer, Gastrointestinal Stromal Tumor, Hepatocellular Carcinoma


The FDA initially approved regorafenib for chemorefractory metastatic colorectal cancer and unresectable gastrointestinal stromal tumor in 2012.

Regorafenib (Stivarga) is an oral multikinase inhibitor approved for metastatic colorectal cancer (mCRC) refractory to fluoropyrimidine-oxaliplatin and irinotecan-based chemotherapy, second line use in metastatic or unresectable gastrointestinal stromal tumor (GIST), and hepatocellular carcinoma (HCC) in patients previously treated with sorafenib.1,2

In 2012, CRC was one of the most common diagnosed cancers worldwide, estimated at 1.36 million new cases and 694,000 fatalities.2 Treatment, management, and overall survival (OS) of patients with mCRC has improved in recent years.

Dosing and Administration

Regorafenib is available in 40 mg tablets, dosed as 160 mg (four, 40 mg tablets) once daily for 3 weeks, followed by a 1-week treatment break.1 Patients should take regorafenib whole with water after a low-fat meal (<600 calories and <30% fat) at the same time daily.1 They should avoid grapefruit juice and St. John’s Wort, as they may increase or decrease blood levels of regorafenib, respectively. Regorafenib does not require renal dosing adjustments.1

FDA Approval

The FDA approved regorafenib for chemorefractory mCRC and GIST on September 27, 2012.1 The CORRECT trial randomized 760 patients to receive regorafenib or placebo and median OS was 6.4 months in the regorafenib group versus 5 months in the placebo group.3 The GRID trial employed regorafenib in patients with progressive metastatic or unresectable GIST despite standard treatment.4 Results showed considerable improvement in progression-free survival in the regorafenib group versus placebo.

The FDA expanded its approval for HCC in patients previously treated with sorafenib on April 27, 2017—the first drug approved for liver cancer in almost 10 years.5 The RESORCE trial found regorafenib improved OS, at 10.6 months in regorafenib group versus 7.8 months in the placebo group.6

Adverse Effects (AEs)

Clinicians should monitor liver function before and during therapy as severe hepatic injury occurred across all regorafenib clinical trials.1 Adjustments or discontinuation may be necessary in patients with repeatedly elevated liver function tests. Common notable AEs include hypertension, hand-foot skin reactions, infection, and diarrhea. Prescribers can reduce doses in 40 mg increments if these AEs become intolerable. The lowest effective dose is 80 mg daily.1

Pregnancy and Lactation

Regorafenib can cause fetal harm and should not be taken during pregnancy. Females of childbearing age and their male partners should use effective contraception during and for 2 months after treatment.1

Breastfeeding is not recommended while taking regorafenib and should be avoided for 2 weeks after the last dose.1

About the Author

Sara L. Tolliday, PharmD, RPh, is a full-time pharmacist at Wentworth-Douglass Hospital, Outpatient Pharmacy, Dover, NH.


1. Bayer Healthcare Pharmaceuticals Inc. STIVARGA® (regorafenib): Official Prescriber Site. Last updated June 2021. Accessed October 4, 2021. www.hcp.stivarga-us.com

2. Dhillon S. Regorafenib: A Review in Metastatic Colorectal Cancer. Drugs. 2018;78(11):1133-1144. doi:10.1007/s40265-018-0938-y.

3. 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.

4. 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.

5. U.S. Food and Drug Administration (FDA). FDA expands approved use of Stivarga to treat liver cancer. April 27, 2017. Accessed October 6, 2021. www.fda.gov/news-events/press-announcements/fda-expands-approved-use-stivarga-treat-liver-cancer

6. 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 [published correction appears in Lancet. 2017 Jan 7;389(10064):36]. Lancet. 2017;389(10064):56-66. doi:10.1016/S0140-6736(16)32453-9.

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