Avastin^® (bevacizumab), in combination with chemotherapy, is the only biologic to significantly improve overall survival (OS) in first-line metastatic non-squamous NSCLC and first- and second-line MCRC¹

NSCLC=non-small cell lung cancer; MCRC=metastatic colorectal cancer.

Progression-free survival (PFS) and response rates (RRs) were also significantly improved in NSCLC and MCRC^1,2*

*Based on investigator assessment (not independently verified) in first-line
metastatic non-squamous NSCLC.²

Review important information regarding the efficacy and safety of Avastin plus PC in NSCLC

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In first- and second-line MCRC, Avastin�in combination with IV 5-FU–based chemotherapy�is the only FDA-approved biologic to demonstrate significant improvements in OS, PFS, and ORR^1,3,4

	Avastin is the only FDA-approved biologic to achieve the primary efficacy endpoints across 3 distinct IV 5-FU–based chemotherapy backbones in MCRC^3-5
	Avastin�when combined with IFL�is the only FDA-approved biologic with an OS benefit prospectively demonstrated in first-line MCRC^1,3

PC=paclitaxel/carboplatin; IV=intravenous; 5-FU=5-fluorouracil; ORR=overall RR; IFL=5-FU/leucovorin/irinotecan.

Indications
Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non�squamous non�small cell lung cancer in combination with carboplatin and paclitaxel.

Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil�based chemotherapy.

Boxed WARNINGS
Gastrointestinal (GI) perforation: Serious and sometimes fatal GI perforation occurs at a higher incidence (up to 2.4%) in Avastin-treated patients compared to controls. Discontinue Avastin for 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. Discontinue in patients with wound dehiscence. Discontinue at least 28 days prior to elective surgery. Do not initiate Avastin for at least 28 days after surgery and until the surgical wound is fully healed.
Hemorrhage: Severe or fatal hemorrhage, hemoptysis, GI bleeding, CNS hemorrhage, and vaginal bleeding are increased in Avastin-treated patients. Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis.

Please click here for additional important safety information

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Boxed WARNINGS

	Gastrointestinal (GI) perforation
	—	Serious and sometimes fatal GI perforation occurs at a higher incidence in Avastin-treated patients compared to controls
	—	The incidences of GI perforation ranged from 0.3% to 2.4% 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
	—	Do not initiate Avastin for at least 28 days after surgery and until the surgical wound is fully healed. The appropriate interval between termination of Avastin and subsequent elective surgery required to reduce the risks of impaired wound healing/wound dehiscence has not been determined
	—	Discontinue Avastin at least 28 days prior to elective surgery and 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. Across indications, the incidence of grade >3 hemorrhagic events among patients receiving Avastin ranged from 1.2% to 4.6%
	—	Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis (>1/2 tsp of red blood)
	—	Discontinue Avastin in patients with serious hemorrhage (ie, requiring medical intervention)

Additional serious adverse events

	Additional serious and sometimes fatal adverse events with increased incidence in the Avastin-treated arm vs control included
	—	Non-GI fistula formation (<0.3%)
	—	Arterial thromboembolic events (grade >3, 2.6%)
	—	Proteinuria (nephrotic syndrome, <1%)
	Additional serious adverse events with increased incidence in the Avastin-treated arm vs control included
	—	Hypertension (grade 3–4, 5%–18%)
	—	Reversible posterior leukoencephalopathy syndrome (RPLS) (<0.1%)
	Infusion reactions with the first dose of Avastin were uncommon (<3%), 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

Most common adverse events

Most common adverse reactions observed in Avastin patients at a rate >10% and at least twice the control arm rate 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 8.4% to 21% of patients because of adverse reactions

Pregnancy warning

	Avastin may impair fertility
	Based on animal data, Avastin may cause fetal harm
	Advise patients of the potential risk to the fetus during and following Avastin and the need to continue adequate contraception for at least 6 months following the last dose of Avastin
	For nursing mothers, discontinue nursing or Avastin, taking into account the importance of Avastin to the mother
	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 thrombus/embolism (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 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 diarrhea (18% vs 13%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), ileus (4% vs 1%), neuropathy�sensory (17% vs 9%), neurologic�other (5% vs 3%), fatigue (19% vs 13%), abdominal pain (8% vs 5%), headache (3% vs 0%), hypertension (9% vs 2%), and hemorrhage (5% vs 1%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in the study

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

References:

1.	Avastin Prescribing Information. Genentech, Inc. May 2012.
2.	Sandler A, Gray R, Perry MC, et al. N Engl J Med. 2006;355:2542-2550.
3.	Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342.
4.	Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544.
5.	Kabbinavar F, Hurwitz H, Fehrenbacher L, et al. J Clin Oncol. 2003;21:60-65.

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