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• • Oncologists Speak on Avastin
  • Efficacy in NSCLC
  • Dosing and Administration
  • NSCLC Resources
  • Safety Information
  • Prescribing Information

Evidence-based dosing

Avastin dosing recommendations in first-line NSCLC

The significant survival benefit achieved with Avastin plus PC in first-line non-small cell lung cancer (NSCLC) treatment has been observed when Avastin was given until disease progression or unacceptable toxicity at the evidence-based dose 15 mg/kg IV every 3 weeks (q3w).¹

Avastin dosing in first-line NSCLC¹

The selection of the 15 mg/kg IV q3w dose was based on the results of a Phase II trial (Study AVF0757g), which compared Avastin plus PC at 2 different doses (15 and 7.5 mg/kg IV q3w) vs a control group (PC alone). A significant increase in time to progression vs control was observed only in the 15 mg/kg IV group (see the Overall Survival section).

15 mg/kg IV q3w is the only dose of Avastin proven to increase OS in first-line advanced non-squamous NSCLC

15 mg/kg IV q3w was proven superior to 7.5 mg/kg IV q3w in a Phase II trial (Study AVF0757g)²

• *Patients in the PC alone arm could cross over to an Avastin arm upon progression.
• ^†P=0.023 vs control arm.
• ^‡P value was not significant vs control arm.

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-treated patients with histology other than squamous cell. As a result, patients with squamous cell histology were excluded from Study E4599.

Continuing Avastin until disease progression or unacceptable toxicity

In Study E4599, patients in the investigational arm received Avastin 15 mg/kg IV q3w plus PC for up to 6 cycles, after which Avastin 15 mg/kg IV q3w alone was continued until disease progression or unacceptable toxicity. Dose reduction of Avastin was not allowed. In the event of unacceptable toxicity, Avastin was either discontinued or suspended. The average duration of treatment in the Avastin plus PC group was 8.9 cycles vs 4.3 cycles in the group that received PC alone.^1,4

Avastin plus PC has been proven to increase OS when given until disease progression or unacceptable toxicity

Avastin was continued until disease progression or unacceptable toxicity in Study E4599^1,3

In Study E4599, patients who were responding or had stable disease after 6 cycles of Avastin plus PC continued on Avastin alone until disease progression or unacceptable toxicity⁴

NCCN recommends continuing bevacizumab following the combination of bevacizumab plus chemotherapy, as investigated in Study E4599^1,3-5

Important treatment considerations—Dose modifications

Discontinue Avastin in patients with GI perforations (GI perforations, fistula formation in the GI tract, intra-abdominal abscess), fistula formation involving an internal organ, wound dehiscence and wound healing complications requiring medical intervention, serious hemorrhage (ie, requiring medical intervention), severe ATE, hypertensive crisis or hypertensive encephalopathy, RPLS (symptoms usually resolve or improve within days, although some patients have experienced ongoing neurologic sequelae), and nephrotic syndrome. Temporarily suspend Avastin for at least 4 weeks prior to elective surgery, severe hypertension not controlled with medical management, moderate to severe proteinuria pending further evaluation, and severe infusion reactions. The safety of resumption of Avastin therapy in patients that experienced RPLS, ATE, and moderate to severe proteinuria is unknown.

Important treatment considerations—Women of childbearing potential

Avastin may impair fertility. Prior to initiation of therapy, advise patients of the potential risk of Avastin to the developing fetus. Counsel patients who become pregnant about the possible risks, including hazard to the fetus and/or loss of pregnancy, of both continued treatment and prolonged exposure following discontinuation, keeping in mind the approximate half-life of Avastin (20 days; range 11–50 days). Patients should also be counseled to continue adequate contraception for at least 6 months following the last dose of Avastin.

Preparing and administering the infusion

The necessary amount of Avastin should be withdrawn and diluted in a total volume of 100 mL of 0.9% Sodium Chloride Injection, USP. Discard any unused portion left in the vial, as the product contains no preservatives. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Avastin infusions should not be administered or mixed with dextrose solutions. Diluted Avastin solutions for infusion may be stored at 2–8°C (36–46°F) for up to 8 hours. DO NOT ADMINISTER AS AN IV PUSH OR BOLUS.¹

Avastin infusion times may be reduced over the course of treatment if tolerated. The initial Avastin dose should be delivered over 90 minutes as an IV infusion following chemotherapy. If the first infusion is tolerated, the second infusion may be administered over 60 minutes. If the 60-minute infusion is tolerated, all subsequent infusions may be administered over 30 minutes.¹

Infusion times¹

In clinical studies, infusion reactions with the first dose of Avastin were uncommon (<3%), and severe reactions occurred in 0.2% of patients. Adequate information on rechallenge is not available. Avastin infusion should be interrupted in all patients with severe infusion reactions and appropriate medical therapy administered.¹

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