Indication

Avastin, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung 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 NSCLC, grade 3–5 (nonhematologic) and grade 4–5 (hematologic) adverse events in Study E4599 occurring at a ≥2% higher incidence in Avastin-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%)

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.

NSCLC=non-squamous non-small cell lung cancer; PC=paclitaxel/carboplatin.

References: 1. Avastin Prescribing Information. Genentech, Inc. 2017. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Non-Small Cell Lung Cancer V.1.2018. © National Comprehensive Cancer Network, Inc 2017. All rights reserved. Accessed November 29, 2017. To view the most recent and complete version of the guideline, go online to NCCN.org.

AVL/082216/0025(3)

www.avastin-hcp.com