View web and mobile version Visit Avastin.com   To advance your care of adult glioblastoma patients with progressive disease following prior therapy The first drug therapy approved in more than a decade for adult GBM patients with progressive disease following prior therapy1,2 Please join Timothy Cloughesy, MD—Director, UCLA Neuro-Oncology Program, and Clinical Professor—for his discussion of Avastin® (bevacizumab) as treatment for adult patients with relapsed glioblastoma (GBM), including his case study of an actual patient enrolled in the pivotal trial for Avastin in GBM. View video Register for important updates about Avastin The first drug therapy approved in more than a decade1,2 Single-agent Avastin demonstrated an objective response for a clinically meaningful duration1-3 The BRAIN (AVF3708g) study1-3   NCI study1,2   ORR=objective response rate; CI=confidence interval; NCI=National Cancer Institute. * ORR and median duration of response were measured by a blinded independent review facility. Indication Avastin is indicated for the treatment of glioblastoma as a single agent for adult patients with progressive disease following prior therapy. The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with Avastin. 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 The BRAIN study was an open-label, multicenter, randomized, noncomparative Phase II study of patients (N=167) with previously treated GBM1-3   — Dosing: Avastin 10 mg/kg as a solution for intravenous (IV) infusion every 2 weeks (q2w) until disease progression or unacceptable toxicity1   — Inclusion criteria: Prior radiotherapy (RT; completed >8 weeks prior) and previous treatment with temozolomide (TMZ); >4 weeks postsurgery; a Karnofsky performance status (KPS) >70 was required1-3   — Exclusion criterion: Active brain hemorrhage1   — Median age, 54 years; 32% female; 81% in first relapse; KPS >90 in 45% of patients and between 70 and 80 in 55% of patients1,3 The NCI study was a Phase II, single-arm, single-institution trial of patients (N=56) with GBM1,2,4   — Dosing: Avastin 10 mg/kg IV q2w until disease progression or unacceptable toxicity1   — Inclusion criteria: Documented disease progression after previous treatment with TMZ and RT; a KPS >60 was required1,2,4   — Median age, 54 years; 54% male; 98% Caucasian; KPS >90 in 68% of patients1 Single-agent Avastin most frequently reported adverse events1,3 Any grade: Infection (55%), fatigue (45%), headache (37%), hypertension (30%), epistaxis (19%), and diarrhea (21%) Grade >3: Infection (10%), fatigue (4%), headache (4%), hypertension (8%), and diarrhea (1%) Review more information about Avastin in GBM Indication Avastin is indicated for the treatment of glioblastoma as a single agent for adult patients with progressive disease following prior therapy. The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with Avastin. 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 GBM Study AVF3708g, in patients receiving Avastin alone, the most frequently reported adverse events were infection (55%), fatigue (45%), headache (37%), hypertension (30%), epistaxis (19%), and diarrhea (21%). Of these, the incidence of grade >3 adverse events was infection (10%), fatigue (4%), headache (4%), hypertension (8%), and diarrhea (1%). Two deaths were possibly related to Avastin: 1 retroperitoneal hemorrhage and 1 neutropenic infection In GBM patients receiving Avastin alone or Avastin plus irinotecan,† the incidences of Avastin-related adverse events (grade 1–4) were bleeding/hemorrhage (40%), epistaxis (26%), CNS hemorrhage (5%), hypertension (32%), venous thromboembolic events (8%), arterial thromboembolic events (6%), wound healing complications (6%), proteinuria (4%), GI perforation (2%), and RPLS (1%). The incidences of grade 3–5 events in these 163 patients were bleeding/hemorrhage (2%), CNS hemorrhage (1%), hypertension (5%), venous thromboembolic events (7%), arterial thromboembolic events (3%), wound healing complications (3%), proteinuria (1%), and GI perforation (2%). Intracranial hemorrhage occurred in 8 of 163 patients; 2 patients had grade 3–4 hemorrhage † Avastin is not approved for use in combination with irinotecan. Please see full Prescribing Information, including Boxed WARNINGS, for additional important safety information. References: 1. Avastin Prescribing Information. Genentech, Inc. December 2011. 2. Data on file. Genentech, Inc. 3. Friedman HS, Prados MD, Wen PY, et al. J Clin Oncol. 2009;27:4733-4740. 4. Kreisl TN, Kim L, Moore K, et al. J Clin Oncol. 2009;27:740-745. 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 or manage your Genentech BioOncology communications, click here. AVA0001045700 (05/12)