Evidence-based Dosing

Avastin dosing recommendations in first-line NSCLC

The significant survival benefit achieved with Avastin plus chemotherapy in first-line NSCLC treatment has been observed when Avastin was given until disease progression or unacceptable toxicity at the evidence-based dose (15 mg/kg q3w).1

Avastin dosing in first-line NSCLC1

The selection of the 15 mg/kg 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 q3w) vs a control group (PC alone). A significant increase in time to progression vs control was observed only in the 15 mg/kg group (see the Overall Survival section). Based on these results, ECOG selected 15 mg/kg q3w as the dose of Avastin in Study E4599.2

Maintaining Avastin until disease progression or unacceptable toxicity

In Study E4599, patients in the investigational arm received Avastin 15 mg/kg q3w plus PC for up to 6 cycles, after which Avastin 15 mg/kg 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. Chemotherapy dose modifications or delays did not impact the administration of Avastin therapy. 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.1,3

Avastin duration per Phase III trial protocols (Study E4599)1

Treatment discontinuation and suspension

  • Permanently discontinue Avastin in patients with GI perforation (GI perforation, fistula formation in the GI tract, intra-abdominal abscess), fistula formation involving an internal organ, wound dehiscence requiring medical intervention, serious bleeding, severe ATE, nephrotic syndrome, hypertensive crisis, or hypertensive encephalopathy

  • In patients developing RPLS, discontinue Avastin and initiate treatment of hypertension if present. Symptoms usually resolve or improve within days, although some patients have experienced ongoing neurological sequelae

  • Temporary suspension is recommended in patients with evidence of moderate to severe proteinuria, in patients with severe hypertension that is not controlled with medical management, and for at least several weeks prior to elective surgery. Avastin should not be resumed until the surgical incision is fully healed

  • Patients who become pregnant while on Avastin therapy should be counseled regarding possible risk to the fetus and/or loss of pregnancy

Important treatment considerations for women of childbearing potential

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 of both continued treatment (including hazard to the fetus and/or loss of pregnancy) and prolonged exposure following discontinuation, keeping in mind the approximate half-life of Avastin (20 days; range 11-50 days).

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

Flexible infusion times1

Avastin Administration

In clinical trials, 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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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.