About Avastin

Avastin Safety Profile in First-line NSCLC

A positive benefit-risk ratio in Study E4599

The safety profile of Avastin in combination with PC was demonstrated in Study E4599.1

Avastin plus PC (first-line NSCLC)1

Severe (grade 3–5) adverse events in Study E4599*
(≥2% higher incidence in the Avastin plus PC arm)

  • *NCI-CTC (Version 2.0) grade 3–5 nonhematologic and grade 4 and 5 hematologic adverse events.

  • GI perforation: in Study E4599, 4 of 427 (0.9%) patients receiving Avastin plus PC developed GI perforation. There were no events reported in the PC alone arm (see Boxed WARNINGS in full Prescribing Information)1

  • Hemorrhage: in Study E4599, severe or fatal hemorrhages, including hemoptysis, GI bleeding, CNS hemorrhage, epistaxis, hematemesis, and vaginal bleeding, occurred in 4.7% of NSCLC patients receiving Avastin plus PC compared with 1.1% of control patients (see Boxed WARNINGS in full Prescribing Information)1

  • Arterial thromboembolic events: the incidence of ATEs was increased in NSCLC patients receiving Avastin plus PC in Study E4599 (3.0% vs 1.4% for PC alone patients); 5 events were fatal in the Avastin plus PC arm compared with 1 event in the PC alone arm1

  • Neutropenia and infection: increased rates of severe neutropenia, febrile neutropenia, and infection with severe neutropenia (including some fatalities) have been observed in patients treated with myelosuppressive chemotherapy plus Avastin1

Patient selection and the risk of hemoptysis

Based on a case-control analysis of the Phase II study (Study AVF0757g) as well as findings from an early stage of Study E4599, certain patients were excluded from the Phase III trial.1

Selection criteria related to hemoptysis (Study E4599)1,2

  • Patients were not excluded from Study E4599 due to tumor location1,2

By using these selection criteria, the incidence of severe and sometimes fatal pulmonary hemorrhage with Avastin plus PC in Study E4599 was 2.3% vs 0.5% with PC alone.1

Histology and patient selection

In the pivotal Phase III trial (Study E4599), tumor histology was characterized by the predominant cell type.1,2 NSCLC patients with mixed-cell–type tumors were eligible for Avastin if the predominant cell type was other than squamous.1,2 The following images present examples of tumor histology from patients who would and would not have been eligible for inclusion in Study E4599.

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

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.

Next: Dosing and Administration

References
  1. Avastin Prescribing Information. Genentech, Inc. March 2008.
  2. Data on file. Genentech, Inc.