About Avastin

Efficacy results from Study E4599

A significant overall survival benefit

With a median overall survival of 12.3 months, a significant increase over PC alone, Avastin plus PC is the first treatment regimen to demonstrate median overall survival >1 year in any Phase III metastatic NSCLC trial. As shown in the Kaplan-Meier graph below, more than half of Avastin-treated patients were alive at 1 year, and 23% remained alive at 2 years.1,2

Median overall survival: 12.3 vs 10.3 months (HR=0.80,* P=0.013)1

  • *95% CI, 0.68 to 0.94.

Longer progression-free survival based on investigator assessment

In addition to the significant survival benefit, Avastin plus PC also demonstrated a significant increase in progression-free survival (PFS). Compared with PC alone, Avastin plus PC increased PFS by 38% (6.2 vs 4.5 months; HR=0.66 [95% CI, 0.57 to 0.77], P<0.001), with more than half of Avastin-treated patients progression free at 6 months. This increase in PFS with Avastin plus PC was investigator-assessed and has not been independently verified.1,2

Important safety information—Study E4599

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

Phase II trial: Study AVF0757g

The design for the definitive Phase III trial (Study E4599) was based on the findings from an earlier randomized, controlled trial. Study AVF0757g was a Phase II trial (N=99) of Avastin plus PC vs PC alone that evaluated Avastin at doses of 7.5 and 15 mg/kg q3w. In this trial, no significant increase in time to progression was seen in the lower dose (7.5 mg/kg q3w) vs the control arm (4.3 vs 4.2 months). However, Avastin-based therapy at a dose of 15 mg/kg q3w resulted in a 76% increase in time to progression vs the control arm (7.4 vs 4.2 months; P=0.023).6 Based on these results, ECOG established 15 mg/kg q3w as the dose of Avastin in Study E4599.2

Efficacy results (Study AVF0757g)3

  • †vs control arm.

Patients in the PC arm were allowed to cross over to Avastin alone at disease progression, and 19 of the 32 patients in this group did so. Among these patients, the median duration of treatment was 12 weeks, and 5 patients received Avastin for more than 6 months. One year after crossover, 47.4% (9 of 19) of these patients were still alive.3

Important safety information—Study AVF0757g

The most common events of any severity (≥10% incidence) in the Avastin plus PC group in Study AVF0757g were nausea, leukopenia, neuropathy, peripheral neuritis, infection, paresthesia, vomiting, diarrhea, thrombocytopenia, and fever. In this trial, the incidence of serious or fatal pulmonary hemorrhage was 31% (4 of 13) in Avastin-treated patients with squamous cell histology and 4% (2 of 53) in Avastin-related patients with histology other than squamous cell. As a result, patients with squamous cell histology were excluded from Study E4599.1

Next: Benefit-risk Ratio

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. Johnson DH, Fehrenbacher L, Novotny WF, et al. J Clin Oncol. 2004;22:2184-2191.