Pharmacological Class:
Kinase inhibitor.
Active Ingredient(s):
Regorafenib 40mg; tablets.
Company
Bayer Healthcare Pharmaceuticals Inc.
Indication(s):
Treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy.
Pharmacology:
Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment.
Clinical Trials:
The clinical efficacy and safety of Stivarga were eva luated in an international, multi-center, randomized (2:1), double-blind, placebo-controlled trial (Study 1) in 760 patients with previously treated metastatic colorectal cancer. The major efficacy outcome measure was overall survival (OS); supportive efficacy outcome measures included progression-free survival (PFS) and objective tumor response rate. Patients were randomized to receive 160mg regorafenib orally once daily (n=505) plus Best Supportive Care (BSC) or placebo (n=255) plus BSC for the first 21 days of each 28-day cycle. Stivarga was administered with a low-fat breakfast that contains <30% fat. Treatment continued until disease progression or unacceptable toxicity.
The study resulted in a statistically significant improvement in overall survival [HR=0.77 (95% CI, 0.64–0.94), two-sided p=0.0102] and progression-free survival [HR=0.49 (95% CI, 0.42–0.58), two-sided p<0.0001] compared to placebo in patients with metastatic CRC whose disease had progressed after approved standard therapies. Median overall survival was 6.4 months with Stivarga vs. 5.0 months with placebo; median PFS was 2.0 months with Stivarga vs. 1.7 months with placebo.
Legal Classification:
Rx
Adults:
Swallow whole with a low-fat breakfast (contains <30% fat). 160mg once daily for the first 21 days of each 28-day cycle; until disease progression or unacceptable toxicity. Dose modifications: see full prescribing information.
Children:
<18 years: not established.
Warnings/Precautions:
Risk of severe hepatotoxicity (may be fatal). Monitor hepatic function before starting and at least every 2 weeks during first 2 months of treatment; interrupt and reduce or discontinue if hepatotoxicity or hepatocellular necrosis occurs. Severe hepatic impairment: not recommended. Increased risk of hemorrhage; permanently discontinue if severe or life-threatening. Interrupt and reduce or permanently discontinue if dermatological toxicity occurs (eg, hand-foot skin reaction [a.k.a. palmar-plantar erythrodysesthesia], rash). Ensure blood pressure is controlled before starting; monitor weekly for the first 6 weeks then every cycle or as clinically indicated; withhold if severe or uncontrolled. Myocardial ischemia/infarction: withhold if new or acute onset develops; resume when resolved. Discontinue if reversible posterior leukoencephalopathy syndrome or GI perforation/fistula develops. Wound healing complications: stop treatment at least 2 weeks before surgery; discontinue if wound dehiscence occurs. Fetal toxicity. Pregnancy (Category D); use effective contraception during treatment and up to 2 months after completion. Nursing mothers: not recommended.
Interaction(s)
Avoid concomitant strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, St. John’s Wort). Avoid concomitant strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, voriconazole). Monitor INR levels with concomitant warfarin.
Adverse Reaction(s)
Asthenia/fatigue, decreased appetite and food intake, hand-foot skin reaction, diarrhea, mucositis, weight loss, infection, hypertension, dysphonia; hepatotoxicity, hemorrhage, GI perforation.
How Supplied:
Tabs—84 (3 x 28)
LAST UPDATED:
11/19/2012
