Avastin, in combination with intravenous 5‑fluorouracil-based chemotherapy, is indicated for the first‑ or second‑line treatment of patients with metastatic colorectal cancer.
Avastin, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second‑line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen.
Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer.
Boxed WARNINGS
Gastrointestinal (GI) perforation
Serious and sometimes fatal GI perforation occurs at a higher incidence in Avastin-treated patients compared to patients treated with chemotherapy
The incidence of GI perforation ranged from 0.3% to 3% across clinical studies
Discontinue Avastin in patients with GI perforation
Surgery and wound healing complications
The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients
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, including hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving Avastin. In clinical studies, the incidence of grade ≥3 hemorrhagic events among patients receiving Avastin ranged from 0.4% to 7%
Do not administer Avastin to patients with serious hemorrhage or a recent history of hemoptysis (≥1/2 tsp of red blood)
Discontinue Avastin in patients who develop grade 3-4 hemorrhage
Additional serious adverse events
Additional serious and sometimes fatal adverse events with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
Arterial thromboembolic events (grade ≥3, 5%, highest in patients with GBM)
Renal injury and proteinuria
Grade 34 proteinuria ranged from 0.7% to 7% in clinical studies
Nephrotic syndrome (<1%)
Additional serious adverse events with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
Venous thromboembolism (grade ≥3, 11% seen in GOG-0240)
Infusion reactions with the first dose of Avastin occurred in <3% of patients, and severe reactions occurred in 0.2% of patients
Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with Avastin
Pregnancy warning
Based on the mechanism of action and animal studies, Avastin may cause fetal harm
Advise female patients that Avastin may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy
Advise females of reproductive potential to use effective contraception during treatment with Avastin and for 6 months after the last dose of Avastin
Advise nursing women that breastfeeding is not recommended during treatment with Avastin and for 6 months following their last dose of treatment
Avastin may impair fertility
Most common adverse events
Across indications, the most common adverse reactions observed in Avastin patients at a rate >10% and at least twice the control arm rate were
Epistaxis
Proteinuria
Lacrimation disorder
Headache
Taste alteration
Back pain
Hypertension
Dry skin
Exfoliative dermatitis
Rhinitis
Rectal hemorrhage
Across all studies, Avastin was discontinued in 8% to 22% of patients because of adverse reactions
Indication-specific adverse events
In first-line MCRC, the most common grade 34 events in Study 2107, which occurred at a ≥2% higher incidence in the Avastin plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)
In second-line MCRC, the most common grade 35 (nonhematologic) and 4–5 (hematologic) events in Study E3200, which occurred at a higher incidence (≥2%) in the Avastin plus FOLFOX4 vs FOLFOX4 groups, were fatigue (19% vs 13%), diarrhea (18% vs 13%), sensory neuropathy (17% vs 9%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), hypertension (9% vs 2%), abdominal pain (8% vs 5%), hemorrhage (5% vs 1%), other neurological (5% vs 3%), ileus (4% vs 1%), and headache (3% vs 0%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study
You may report side effects to the FDA at (800) FDA-1088 orwww.fda.gov/medwatch.
You may also report side effects to Genentech at (888) 835-2555.
Please see accompanying full Prescribing Information, includingBoxed WARNINGS, for additional important safety information.