160x600

Indications

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 3–4 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)
Hypertension (grade 3–4, 5%–18%)
Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
Congestive heart failure (CHF) (1%)
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 studies, the most common adverse reactions observed in Avastin patients at a rate >10% 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 3–4 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 3–5 (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
When continued beyond first progression in MCRC, no new safety signals were observed in the TML study (ML18147) when Avastin was administered in second-line MCRC patients who progressed on an Avastin containing regimen in first-line MCRC. The safety data was consistent with the known safety profile established in first- and second-line MCRC

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.

You may also report side effects to Genentech at (888) 835-2555.

Please see full Prescribing Information, including Boxed WARNINGS, for additional important safety information.

First-line Study 2107 was a double-blind, controlled clinical trial in patients with previously untreated MCRC.^1,2

Chemotherapy combinations included either an irinotecan- or oxaliplatin-containing regimen.¹

The TML study was a prospective, randomized, controlled clinical trial in second-line patients previously treated with Avastin.^1,2

References: 1. Avastin Prescribing Information. Genentech, Inc. 2017. 2. Data on file. Genentech, Inc. 3. Bennouna J, Sastre J, Arnold D, et al. Lancet Oncol. 2013;14:29–37.