Visit Avastin.com       Please join John Marshall, MD—Chief of Division of Hematology/Oncology at Georgetown University and Associate Director of Clinical Research at Lombardi Comprehensive Cancer Center—for his engaging discussion of patients appropriate for treatment with Avastin® (bevacizumab) plus intravenous (IV) 5-fluorouracil (5-FU)–based therapy for first- or second-line metastatic colorectal cancer (MCRC). View patient profiles video Experience that matters: Avastin is the only FDA-approved biologic with significant overall survival (OS) improvements in both first- and second-line MCRC1-3 The patients featured are hypothetical in nature and represent those who are appropriate for Avastin plus IV 5-FU–based chemotherapy. Sandra: 56-year-old female Wild-type k-ras; unresectable lung metastasis; performance status (PS) 0; type 2 diabetes; current medications: metformin, amlodipine Data from pivotal Study 2107 support the safety and efficacy of Avastin in first-line MCRC2 Avastin has been FDA-approved for use in combination with IV 5-FU–based therapy, such as FOLFIRI and FOLFOX1   Indication 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   4.7-month increase in median OS with Avastin plus IFL1,2,4 FOLFIRI=5-FU/leucovorin (LV)/irinotecan; FOLFOX4=5-FU/LV/oxaliplatin; IFL=5-FU/LV/irinotecan; HR=hazard ratio; CI=confidence interval. Alex: 84-year-old male Sigmoid adenocarcinoma (positive colonoscopy, computed tomography scan); unresectable liver metastases; transient ischemic attack 14 months prior to diagnosis; PS 1; current medications: aspirin 81 mg qd, finasteride Data from prespecified subgroup analyses of pivotal Study 2107 support the consistent benefit of Avastin in combination with IV 5-FU–based therapy across multiple patient subgroups2 OS demonstrated across a broad range of prespecified subgroups in first-line MCRC1,2,4* qd=once a day; q2w=every 2 weeks; ECOG=Eastern Cooperative Oncology Group. * All were prespecified analyses, with the exception of the liver-only disease subgroup analysis. Additional prespecified subgroups with survival increases included age <40, ages 40–64, race, location of primary tumor, duration of metastatic disease, baseline albumin, baseline alkaline phosphatase, baseline lactate dehydrogenase, duration of disease, sum of the longest diameters of target lesions, and prior radiotherapy.4 † Eligible patients had an ECOG PS of 0 or 1, with less than 1% (n=3) of the study population having an ECOG score of >1.4 ‡ The organs with the most frequent occurrence of metastatic disease were liver (78%), lung (48%), and lymph nodes (25%).4 § Based on an exploratory analysis of prospectively collected data.4 Carla: 66-year-old female Treatment history of adjuvant FOLFOX4 resulting in 36 months of disease-free survival; upon metastatic relapse, she received irinotecan-based standard-of-care therapy resulting in 10 months progression free; PS 1; current medication: adalimumab Data from pivotal Study E3200 support the efficacy and safety of Avastin in second-line MCRC in combination with IV 5-FU–based therapy3 Significant increase in median OS with Avastin plus FOLFOX4 in pivotal Study E32001,3,4 View complete KOL presentation of MCRC patient profiles 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, 2.4%)   — Proteinuria including 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 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%) Please see full Prescribing Information, including Boxed WARNINGS, for additional important safety information. References: 1. Avastin Prescribing Information. Genentech, Inc. December 2011. 2. Hurwitz H, Fehrenbacher L, Novotny W, et al. N Engl J Med. 2004;350:2335-2342. 3. Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544. 4. Data on file. Genentech, Inc.           Privacy Policy | Terms and Conditions | Contact Genentech® This e-mail is intended for U.S. healthcare professionals only. © 2012 Genentech USA, Inc. All rights reserved. Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990 To unsubscribe from the Genentech BioOncology mailing list, please click here. AVA0000618500 (01/12)