Stivarga comes in 40 mg tablets. Once opened, it must be used within 28 days. Stivarga must be stored in the bottle that it comes in, the desiccant must remain in the bottle; keep bottle tightly sealed. Do not store in a daily or weekly pill box.

Bayer’s Stivarga (regofarenib)  is a new drug that that is approved for GIST in the United States for third-line treatment when Gleevec and Sutent are no longer working.

The three primary side effects of Stivarga reported in a clinical trial were hand foot syndrome, hypertension and diarrhea.

Hand foot syndrome is characterized by blisters or a rash on your hands and feet. About 20% of participants in the trial reported hand foot syndrome.

Hypertension was the second primary side effect of Stivarga, with 30 to 59% of patients developing high blood pressure. This is a side effect that needs to be treated and monitored closely by your doctor.

Diarrhea was reported by 40% of participants in the clinical trial.

Other side effects include:

  • Wound healing problems – You should stop Stivarga at least 2 weeks before any planned surgery.
  • Fetal toxicity – Stivarga can cause fetal harm when administered to a pregnant woman.
  • Decreased appetite and food intake
  • Weight loss
  • A change in voice (often described by patients as hoarseness)
  • Some patients report some hair loss

Rare, but serious side effects of Stivarga include:

  • Liver damage – may be severe or life threatening. Patients need to undergo monitoring and immediately report signs or symptoms of liver damage to their health care provider. Liver function tests (ALT, AST and bilirumin) must be checked before starting Stivarga, and at least every two weeks for the first two months of treatment. Thereafter, monitor monthly or more frequently as clinically indicated (source: FDA prescribing information).
  • Severe bleeding.
  • Myocardial ischemia and infarction.
  • Reversible Posterior Leukoencephalopathy Syndrome (RPLS).
  • Bowel perforation

Laboratory Test Abnormalities

Stivarga can affect a number of lab tests. In most cases this effect is not severe (less than Grade 3). The percentage of patients having any grade of these abnormalities in the phase III GIST trial (GRID trial) is reported in parentheses below. For full results, including percentages of more serious abnormalities, see the FDA prescribing information.

Blood and Lymphatic system

  • Anemia (not reported in the GIST trial, but reported as 79% in the colorectal trial)
  • Thrombocytopenia (13%)
  • Neutropenia (16%)
  • Lymphopenia (30%)

Metabolism and Nutrition

  • Hypocalcemia (17%)
  • Hypokalemia (21%)
  • Hyponatremia (not reported in GIST trial, 30% in colorectal trial)
  • Hypophosphatemia (55%)

Liver

  • Hyperbilirubinemia (33%)
  • Increased AST (58%)
  • Increased ALT (39%)

Renal and urinary

  • Proteinuria (33%)

Investigations

  • Increased INR (not reported in GIST trial, 24% in colorectal trial)
  • Increased Lipase (14%)
  • Increased Amylase (not reported in GIST trial, 26% in colorectal trial)

See Stivarga prescribing information (PDF)

See Stivarga patient information – PDF – Bayer Website (less technical, but less detailed than the prescribing information)

Side effects reported in phase III trial of regorafenib vs. placebo

  Regorafenib (n=131)Any grade (all severities) Placebo (n=66)Any grade
Any event

98%

68%

Hand-foot skin reaction

56%

14%

Hypertension

49%

17%

Diarrhea

40%

5%

Fatigue

39%

27%

Oral mucositis

38%

8%

Alopecia (hair loss)

24%

2%

Rash, maculopapular

18%

3%

Nausea

16%

9%

Constipation

15%

6%

Myalgia

14%

9%

Voice alteration

11%

3%

Drug-related adverse events in ≥ 10% of GIST patients during double-blind treatment period. Adapted from: Demetri GD, Reichardt P, Kang Y-K, Blay J-Y, Rutkowski P, Gelderblom H, Hohenberger P, Leahy M, Von Mehren M, Joensuu H, Badalamenti G, Blackstein M, Le Cesne A, Schöffski P, Maki RG, Bauer S, Nguyen BB, Xu J, Nishida T, Chung J, Kappeler C, Kuss I, Laurent D, Casali PG: 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. The Lancet2012.

 

Jerry Call
Author: Jerry Call