Kidney Cancer: Avastin Safety Profile

Metastatic renal cell carcinoma (mRCC)
Avastin, in combination with interferon alfa, is indicated for the treatment of metastatic renal cell carcinoma.

Phase III AVOREN study: Avastin plus interferon alfa (IFN)[1]

Selected grade 3–5 adverse events in mRCC patients (≥2% higher incidence in the Avastin arm)[1]

Adverse event Avastin + IFN (%)
(n=337)
Placebo + IFN (%)
(n=304)
Fatigue 13 8
Asthenia 10 7
Proteinuria 7 0
Hypertension 6 1
Hemorrhage* 3 0.3

*Including epistaxis, small intestinal hemorrhage, aneurysm ruptured, gastric ulcer hemorrhage, gingival bleeding, hemoptysis, hemorrhage intracranial, large intestinal hemorrhage, respiratory tract hemorrhage, and traumatic hematoma.

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage

Adverse events (all grades) occurring at ≥5% higher incidence in the Avastin arm[1]

Adverse event Avastin + IFN (%)
(n=337)
Placebo + IFN (%)
(n=304)
Decreased appetite 36 31
Fatigue 33 27
Hypertension 28 9
Epistaxis 27 4
Headache 24 16
Diarrhea 21 16
Weight decreased 20 15
Proteinuria 20 3
Myalgia 19 14
Back pain 12 6
Dysphonia 5 0
  • The following adverse events were reported at a 5-fold more frequency in the IFN plus Avastin arm compared to IFN alone and not represented in the table above: gingival bleeding (13 patients vs 1 patient), rhinitis (9 vs 0), blurred vision (8 vs 0), gingivitis (8 vs 1), gastroesophageal reflux disease (8 vs 1), tinnitus (7 vs 1), tooth abscess (7 vs 0), mouth ulceration (6 vs 0), acne (5 vs 0), deafness (5 vs 0), gastritis (5 vs 0), gingival pain (5 vs 0), and pulmonary embolism (5 vs 1)[1]
  • Adverse events were consistent with those previously reported for Avastin[1,14]
  • Deaths due to adverse events were reported in 8 patients (2%) who received Avastin and in 7 (2%) of those who did not receive Avastin[14]
    • Among patients who received Avastin, 3 deaths (<1%) were possibly related to Avastin 
  • Flexible IFN dose modification allowed for IFN toxicity management in AVOREN[3,14]