Indications

Avastin^® (bevacizumab) injection, for intravenous use, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan, is indicated for the treatment of patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens.

Avastin, in combination with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by Avastin as a single agent, is indicated for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal 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
• 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 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
  • 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 events

• In psOC, grade 3 or 4 adverse reactions in the OCEANS study occurring at a higher incidence (≥2%) in 247 patients receiving Avastin plus carboplatin and gemcitabine (chemotherapy), compared to 233 patients receiving placebo plus chemotherapy, were thrombocytopenia (40% vs 34%), nausea (4% vs 1.3%), fatigue (6% vs 4%), headache (4% vs 0.9%), proteinuria (10% vs 0.4%), dyspnea (4% vs 1.7%), epistaxis (5% vs 0.4%), and hypertension (17% vs 0.9%)
• In psOC, grade 3 or 4 adverse reactions in the GOG-0213 study occurring at a higher incidence (≥2%) in 325 patients receiving Avastin plus carboplatin and paclitaxel (chemotherapy), compared to 332 patients receiving chemotherapy alone, were hypertension (11% vs 0.6%), fatigue (8% vs 3%), febrile neutropenia (6% vs 3%), proteinuria (8% vs 0%), abdominal pain (6% vs 0.9%), hyponatremia (4% vs 0.9%), headache (3% vs 0.9%), and pain in extremity (3.4% vs 0%)
• In prOC, grade 3–4 adverse reactions in AURELIA occurring at a higher incidence (≥2%) in 179 patients receiving Avastin plus chemotherapy, compared to 181 patients receiving chemotherapy alone, were hypertension (6.7% vs 1.1%) and palmar-plantar erythrodysaesthesia syndrome (4.5% vs 1.7%)

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.

AVY/011918/0006  (04/18)

www.avastin-hcp.com