About Avastin

Avastin-based Therapy in First-line NSCLC: A Significant Survival Benefit

Pivotal Phase III trial: ECOG Study E4599

The clinical benefits of Avastin-based therapy in first-line treatment of NSCLC were demonstrated in Study E4599, a large, Phase III trial conducted by the Eastern Cooperative Oncology Group (ECOG). In this multicenter trial (N=878), chemotherapy-naïve patients were randomized to receive PC alone or with Avastin at a dose of 15 mg/kg q3w. Patients received Avastin with PC for up to 6 cycles, after which Avastin 15 mg/kg q3w was continued alone until disease progression or unacceptable toxicity. The primary endpoint in Study E4599 was overall survival.1

E4599 study design1

  • *Included patients with locally advanced, metastatic, or recurrent NSCLC.

The study population consisted of patients with locally advanced, metastatic, or recurrent NSCLC, including patients with both stage IIIB (with pleural effusion) and stage IV disease. Key ECOG-determined NSCLC exclusion criteria were squamous cell histology, mixed-cell–type tumors with predominant squamous cell histology, CNS metastases, current use of therapeutic anticoagulants (INR >1.5), history of gross hemoptysis (≥1/2 tsp of red blood), or unstable angina.1 Considering these selection criteria, a large percentage of first-line NSCLC patients would be eligible for Avastin.2

Key patient characteristics in Study E45993

Histological considerations with Avastin in NSCLC

In Study E4599, tumor histology was determined by metastatic tumor aspirates or biopsy tumor histology. Patients with mixed-cell–type tumors were eligible for Avastin if the predominant cell type was other than squamous. Patients were not excluded from Study E4599 due to tumor location.1,3 Please see the Benefit-risk Ratio section for more detailed information about histology and patient selection.

Important safety information—Hemorrhage

Severe, and in some cases fatal, pulmonary hemorrhage has occurred 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 severe hemorrhage (ie, requiring medical intervention) and initiate aggressive medical management.1

Next: Overall Survival

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.