In this section:

Established efficacy and safety of Avastin plus IFN in mRCC

Significant first-line improvement in progression-free survival (PFS) and objective response rate (ORR) in a range of patients1*

In the AVOREN study, Avastin plus IFN improved median PFS and ORR over IFN alone.1

  • Avastin plus IFN improved median PFS by 89% over placebo plus IFN (10.2 months vs 5.4 months, hazard ratio [HR]=0.60, P<0.0001)1

  • PFS benefit of Avastin plus IFN was observed as early as 2 months and was sustained through the duration of the study1,2

  • Median overall survival (OS) with Avastin plus IFN was 23 months, a nonsignificant increase vs placebo plus IFN (21 months, HR=0.86, P=0.1291)1-3

    • Availability of active subsequent therapies may have confounded the ability to detect a statistically significant OS advantage2

  • Avastin plus IFN more than doubled ORR vs placebo plus IFN (30% vs 12%, P<0.0001), as confirmed by an independent review facility1,4

  • IFN dose reduction or discontinuation was allowed in AVOREN per protocol2,4

  • Avastin plus IFN has an established safety profile in mRCC1

  • *AVOREN included patients in favorable, intermediate, and poor risk groups.

Boxed WARNINGS

Gastrointestinal perforation: Occurs in up to 2.4% of Avastin-treated patients. Discontinue Avastin for gastrointestinal perforation.

Surgery and wound healing complications: 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, gastrointestinal bleeding, CNS hemorrhage, and vaginal bleeding are increased in Avastin-treated patients. Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis.

Bevacizumab plus IFN: NCCN†-recommended for the treatment of mRCC5

The NCCN RCC guidelines include bevacizumab plus IFN as a recommended first-line treatment for patients with predominant clear cell histology. Bevacizumab plus IFN is the only NCCN category 1–recommended intravenous (IV) therapy for mRCC patients in good or intermediate risk groups. Bevacizumab is also recommended by NCCN as a subsequent therapy in mRCC.

  • †National Comprehensive Cancer Network.

Indication

Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

Boxed WARNINGS and additional important safety information

  • 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 dehiscence 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 and sometimes fatal adverse events for which the incidence was increased in the Avastin-treated arm vs control included non-GI fistula formation (≤0.3%), arterial thromboembolic events (grade ≥3, 2.4%), and proteinuria including nephrotic syndrome (<1%). Additional serious adverse events for which the incidence was increased in the Avastin-treated arm vs control included hypertension (grade 3–4, 5%–18%) and 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

  • The most common adverse reactions observed in Avastin patients at a rate >10% and at least twice the control arm rate were epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis. Across all studies, Avastin was discontinued in 8.4% to 21% of patients because of adverse reactions

  • The most common grade 3–5 adverse events in AVOREN, occurring at a ≥2% higher incidence in Avastin-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%), and hemorrhage (3% vs 0.3%)

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

Next: AVOREN Study Design

References
  1. Avastin Prescribing Information, Genentech, Inc. July 2009.
  2. Escudier B, Pluzanska A, Koralewski P, et al. Lancet. 2007;370:2103-2111.
  3. Escudier B, Bellmunt J, Negrier S, et al. Slides presented at: Annual Meeting of the American Society of Clinical Oncology; May 29–June 2, 2009; Orlando, FL.
  4. Data on file. Genentech, Inc.
  5. The NCCN Kidney Cancer Clinical Practice Guidelines in Oncology (Version 2.2009). ©2009 National Comprehensive Cancer Network, Inc. http://www.nccn.org. Accessed July 27, 2009. To view the most recent and complete version of the guidelines, go online to www.nccn.org.