MVASI™ WAS APPROVED BASED ON A TOTALITY OF EVIDENCE, INCLUDING A COMPARATIVE CLINICAL TRIAL^1,2

• Gastrointestinal (GI) perforation
  • Serious and sometimes fatal GI perforation occurred at a higher incidence in bevacizumab-treated patients compared to patients treated with chemotherapy
  • The incidence of GI perforation ranged from 0.3% to 3% across clinical studies
  • Discontinue MVASI™ 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 bevacizumab-treated patients
  • Withhold MVASI™ for at least 28 days prior to elective surgery. Do not administer MVASI™ 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 bevacizumab. In clinical studies, the incidence of grade ≥3 hemorrhagic events among patients receiving bevacizumab ranged from 0.4% to 7%
  • Do not administer MVASI™ to patients with serious hemorrhage or a recent history of hemoptysis (≥1/2 tsp of red blood)
  • Discontinue MVASI™ in patients who develop grade 3–4 hemorrhage
• Additional serious and sometimes fatal adverse events with increased incidence in the bevacizumab-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 bevacizumab-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 bevacizumab 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 MVASI™

Pregnancy warning

• Based on the mechanism of action and animal studies, MVASI™ may cause fetal harm when administered to pregnant women
• Advise female patients that MVASI™ 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 MVASI™ and for 6 months after the last dose
• Advise nursing women that breastfeeding is not recommended during treatment with MVASI™ and for 6 months following their last dose of treatment
• MVASI™ may impair fertility

Most common adverse events

• Across studies, the most common adverse reactions observed in bevacizumab-treated 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, bevacizumab was discontinued in 8% to 22% of patients because of adverse reactions

Indication-specific adverse events

• In CC, grade 3 or 4 adverse reactions in Study GOG-0240, occurring at a higher incidence (≥2%) in 218 patients receiving bevacizumab plus chemotherapy compared to 222 patients receiving chemotherapy alone, were abdominal pain (12% vs 10%), diarrhea (6% vs 3%), anal fistula (4% vs 0%), proctalgia (3% vs 0%), urinary tract infection (8% vs 6%), cellulitis (3% vs 0.5%), fatigue (14% vs 10%), hypertension (11% vs 0.5%), thrombosis (8% vs 3%), hypokalemia (7% vs 4%), hyponatremia (4% vs 1%), dehydration (4% vs 0.5%), neutropenia (8% vs 4%), lymphopenia (6% vs 3%), back pain (6% vs 3%), and pelvic pain (6% vs 1%)
• In mRCC, the most common grade 3–5 adverse events in AVOREN, occurring at a >2% higher incidence in bevacizumab-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%, including hypertension and hypertensive crisis), and hemorrhage (3% vs 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)
• In rGBM Study EORTC 26101, 22% of patients discontinued treatment in the bevacizumab with lomustine arm due to adverse reactions compared with 10% of patients in the lomustine arm. In patients receiving bevacizumab with lomustine, the adverse reaction profile was similar to that observed in other approved indications
• In NSCLC, grade 3–5 (nonhematologic) and grade 4–5 (hematologic) adverse events in Study E4599 occurring at a ≥2% higher incidence in bevacizumab-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thromboembolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%)
• In first-line mCRC, the most common grade 3–4 events in Study 2107, which occurred at a ≥2% higher incidence in the bevacizumab 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 bevacizumab 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 Amgen at 1-800-772-6436.

Please see full Prescribing Information for additional Important Safety Information.