About Avastin

Avastin-based Therapy: A Significant Advance in First-line NSCLC Treatment

Efficacy overview

In a pivotal Phase III trial in the first-line treatment of non-small cell lung cancer (NSCLC) (ECOG Study E4599), Avastin plus paclitaxel/carboplatin (PC) demonstrated important first-line clinical benefits over PC alone, including a significant increase in overall survival. With these results, Avastin is the first biologic therapy proven to extend survival when added to a conventional chemotherapy doublet in first-line NSCLC treatment.1,2

Avastin-based therapy: Increased median overall survival vs paclitaxel/carboplatin alone1

The significant survival benefit of Avastin-based therapy in NSCLC was achieved when Avastin was given until disease progression. Per the pivotal trial protocol, patients in the investigational arm received Avastin 15 mg/kg q3w plus chemotherapy for up to 6 cycles, after which patients continued to receive Avastin 15 mg/kg q3w alone until disease progression or unacceptable toxicity. Chemotherapy dose modifications or delays did not impact the administration of Avastin therapy.1,3

Safety overview

In pivotal trials, the most serious adverse events associated with Avastin were GI perforation, wound healing complication, hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, neutropenia and infection, nephrotic syndrome, and congestive heart failure. The most common severe (grade 3–5) adverse events in Study E4599, occurring at a ≥2% higher incidence in Avastin-treated patients vs controls, were neutropenia, fatigue, hypertension, infection, and hemorrhage.1 (Please see full Prescribing Information, including Boxed WARNINGS, and the Safety Information section for additional safety information.)

Avastin has demonstrated a positive benefit-risk ratio in NSCLC for appropriately selected patients (see the E4599 Study Design and Benefit-risk Ratio sections for key exclusion criteria). In Study E4599, Avastin was associated with an increased risk of severe and sometimes fatal pulmonary hemorrhage (2.3% of Avastin-treated patients vs 0.5% of control patients).1

A recognized clinical advance for appropriate patient types

In consideration of the clinical benefits demonstrated in the first-line treatment of metastatic NSCLC, Avastin plus PC is now recognized by NCCN as a preferred treatment among Avastin-eligible patients in this disease setting.4

Established as a standard of care in first-line NSCLC

Established as a standard of care in first-line NSCLC


Recognized as a standard of care in first-line NSCLC for appropriate patient types

Established as a standard of care in first-line NSCLC

  • †National Comprehensive Cancer Network.

Additionally, per Sandler et al (ASCO 2005), "[Avastin plus PC] is now the ECOG reference standard for the first-line treatment of advanced, non-squamous cell NSCLC."9

Next: E4599 Study Design

Boxed WARNINGS and Additional Important Safety Information

Gastrointestinal (GI) perforation: Avastin administration can result in the development of GI perforation, in some cases resulting in fatality. GI perforation, sometimes associated with intra-abdominal abscess, occurred throughout treatment with Avastin. Permanently discontinue Avastin therapy in patients with GI perforation.

Wound healing complication: Avastin administration can result in the development of wound dehiscence, in some instances resulting in fatality. Permanently discontinue Avastin therapy in patients with wound dehiscence requiring medical intervention. The appropriate interval between termination of Avastin and subsequent elective surgery has not been determined.

Hemorrhage: Severe, and in some cases fatal, pulmonary hemorrhage can occur in patients with NSCLC treated with chemotherapy and Avastin. Do not administer Avastin to patients with recent hemoptysis (≥1/2 tsp of red blood). Permanently discontinue Avastin in patients with serious hemorrhage and initiate aggressive medical management.

Additional serious adverse events included non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, neutropenia and infection, nephrotic syndrome, and congestive heart failure.

The most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events that may have occurred in Avastin indications (first-line NSCLC, first- and second-line MCRC) included neutropenia, fatigue, hypertension, infection, hemorrhage, asthenia, abdominal pain, pain, deep vein thrombosis, intra-abdominal thrombosis, syncope, diarrhea, constipation, leukopenia, nausea, vomiting, dehydration, ileus, neuropathy–sensory, neurologic–other, and headache.

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

References
  1. Avastin Prescribing Information. Genentech, Inc. March 2008.
  2. Sandler A, Gray R, Perry MC, et al. N Engl J Med. 2006;355:2542-2550.
  3. Data on file. Genentech, Inc.
  4. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology-v.2.2008. Non-Small Cell Lung Cancer. Available at www.nccn.org/professionals/physician_gls/PDF/nscl.pdf. Accessed February 8, 2008.
  5. Breathnach OS, Freidlin B, Conley B, et al. J Clin Oncol.2001; 19: 1734-1744.
  6. Food and Drug Administration. Approved Oncology Drugs with Approved Indications. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist. Accessed July 23, 2007.
  7. Schiller JF, Harrington D, Belani CP, et al. N Eng J Med, 2002; 346: 92-98.
  8. Tong RT, Boucher Y, Kozin SV, et al. Cancer Res. 2004; 64:3731-3736.
  9. Sandler AB, Gray R, Brahmer J, et al. A randomized phase III trial of paclitaxel plus carboplatin with or without bevacizumab in patients with advanced non-squamous non-small cell lung cancer: An Eastern Cooperative Oncology Group Trial—E4599. Slides presented at: American Society of Clinical Oncology; May 13-17, 2005; Orlando, Fla.