View web and mobile version Visit Avastin.com Avastin® (bevacizumab) plus intravenous (IV) 5-fluorouracil (5-FU)–based therapy: A foundation for overall survival (OS) in first-line metastatic colorectal cancer (MCRC) Avastin plus multiple IV 5-FU–containing chemotherapies The only FDA-approved biologic with a prospectively demonstrated OS benefit in first-line MCRC1-3 Study 2107 demonstrated a substantial magnitude of benefit for a first-line MCRC trial1,2 4.7-month increase in median OS with Avastin plus IFL vs placebo plus IFL: 20.3 vs 15.6 months, respectively (HR=0.66 [95% CI, 0.54–0.81], P<0.001)1,3 IFL=5-FU/leucovorin (LV)/irinotecan; HR=hazard ratio; CI=confidence interval. The only FDA-approved biologic to prospectively demonstrate statistically significant improvements in progression-free survival (PFS) and overall response rates (ORRs) in first-line MCRC1,2 4.4-month increase in median PFS with Avastin plus IFL vs placebo plus IFL: 10.6 vs 6.2 months, respectively (HR=0.54 [95% CI, 0.45–0.66], P<0.001)1-3 Avastin plus IFL resulted in a significant increase in ORR vs placebo plus IFL: 45% vs 35%, respectively (P<0.01)1,2 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   Retrospective k-ras analysis of available tissue samples from a subgroup of patients enrolled in Study 2107 (n=230; 28% of the overall population)4 HRs were consistent with those in the overall population, regardless of k-ras status4 k-ras status does not predict clinical benefit from Avastin plus IV 5-FU-based therapy4 These findings have not been confirmed prospectively in a large clinical trial4 Chemo options with Avastin: The only biologic to achieve the primary efficacy endpoints across 3 distinct IV 5-FU–based chemotherapy backbones in MCRC2,5,6 IFL (Phase III Study 2107; primary endpoint: OS) FOLFOX4 (Phase III Study E3200; primary endpoint: OS) IV 5-FU/LV (Phase II Study 0780; coprimary endpoint: Time to progression [TTP]*) FOLFOX4=5-FU/LV/oxaliplatin. * Study 0780 (N=104): Coprimary endpoints=TTP and response rate (RR). TTP (9.0 vs 5.2 months, P=0.005) was significantly better for patients receiving Avastin (5 mg/kg solution for IV infusion) plus IV 5-FU/LV vs IV 5-FU/LV alone. RR in the pooled analysis (Avastin 5 mg/kg and 10 mg/kg plus IV 5-FU/LV vs IV 5-FU/LV alone) was 32% vs 17%, respectively—a nonsignificant difference. 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 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. Please click here for more information about Avastin in MCRC 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. Data on file. Genentech, Inc. 4. Hurwitz HI, Yi J, Ince W, et al. Oncologist. 2009;14:1-7. 5. Giantonio BJ, Catalano PJ, Meropol NJ, et al. J Clin Oncol. 2007;25:1539-1544. 6. Kabbinavar F, Hurwitz H, Fehrenbacher L, et al. J Clin Oncol. 2003;21:60-65. Privacy Policy | Terms and Conditions | Contact Genentech® This email 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. AVA0001092100 (05/12)