Indications

Avastin, in combination with intravenous 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.

Serious adverse reactions (Warnings and Precautions)

• Serious and sometimes fatal adverse reactions with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
  • Gastrointestinal (GI) perforation ranged from 0.3% to 3% of patients across clinical studies
  • Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
  • Arterial thromboembolic events (Grade ≥3, 5%, highest in patients with GBM)
  • The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients
  • Hemorrhage (Grade 3–5) ranged from 0.4% to 7% of patients across clinical studies
  • Renal injury and proteinuria
    • Grade 3–4 proteinuria ranged from 0.7% to 7% in clinical studies
    • Nephrotic syndrome (<1%)
• Additional serious adverse reactions 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): Grade ≥3 left ventricular dysfunction (1%)
• Infusion-related reactions with the first dose of Avastin occurred in <3% of patients, and severe reactions occurred in 0.2% of patients
• Avoid use in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
• Inform females of reproductive potential of the risk of ovarian failure prior to initiating 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 not to breastfeed during treatment with Avastin and for 6 months following their last dose of treatment
• Avastin may impair fertility

Most common adverse reactions

• Across studies, the most common adverse reactions observed in Avastin patients at a rate >10% were:
  • Epistaxis
  • Headache
  • Hypertension
  • Rhinitis
  • Proteinuria
  • Taste alteration
  • Dry skin
  • Rectal hemorrhage
  • Lacrimation disorder
  • Back pain
  • Exfoliative dermatitis
• Across all studies, Avastin was discontinued in 8% to 22% of patients because of adverse reactions

Indication-specific adverse reactions

• In first-line MCRC, the most common Grade 3–4 reactions 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) reactions 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 or www.fda.gov/medwatch.

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

Please see full Prescribing Information for additional important safety information.

References: 1. Avastin Prescribing Information. Genentech, Inc. 2019. 2. Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342.

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AVP/101018/0034(1)

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