Lung Cancer: Avastin Dosing and Usage
First-line non-squamous non-small cell lung cancer (NSCLC)
Avastin, in combination with carboplatin and paclitaxel, is indicated for the first‑line treatment of patients with unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer.
Avastin dosing in first-line advanced nsNSCLC
In advanced nsNSCLC, Avastin is administered as a solution for intravenous (IV) infusion at the following dose and schedule:
|Tumor type||Chemotherapy||Avastin dose||Avastin schedule|
|NSCLC*||Paclitaxel/carboplatin||15 mg/kg IV||Every 3 weeks|
*15 mg/kg IV dose evaluated in first-line locally advanced or metastatic nsNSCLC in combination with paclitaxel/carboplatin (PC). Avastin plus PC was given for up to 6 cycles, after which Avastin was continued alone until disease progression or unacceptable toxicity.
- 15 mg/kg IV every 3 weeks is the only dose of Avastin to demonstrate significantly increased overall survival (OS) in first-line advanced nsNSCLC
Important treatment considerations—Women of childbearing potential
- Avastin increases the risk of ovarian failure and may impair fertility. Inform females of reproductive potential of the risk of ovarian failure prior to the first dose of Avastin
- Long-term effects of Avastin exposure on fertility are unknown
- Patients should also use effective contraception during treatment and for 6 months following the last dose of Avastin
- Nursing mothers should not breastfeed during treatment and for 6 months following their last dose of treatment
Duration of Avastin in nsNSCLC
The FDA-approved Prescribing Information addresses the duration of Avastin treatment: Patients should continue treatment until disease progression or unacceptable toxicity.
Survival benefits were seen with Avastin when continued until disease progression or unacceptable toxicity
- The OS results seen in Study E4599 were achieved with Avastin given until disease progression or unacceptable toxicity
- 60% of patients receiving Avastin plus PC in Study E4599 completed 6 cycles of therapy (vs 44% in the PC alone arm), thereby making those patients eligible to continue Avastin alone until disease progression or unacceptable toxicity
- In Study
E4599, patients in the Avastin plus PC arm received an average of
8.9 cycles of study treatment
- Study treatment consisted of either Avastin plus PC or Avastin alone after PC was discontinued
Important treatment considerations—dose modifications
No dose reductions for Avastin are recommended.
Dose Modifications for Adverse Reactions
|Adverse reaction||Severity||Dosage modification|
|Gastrointestinal perforation and fistulae|| ||Discontinue Avastin|
|Wound healing complications|| ||Discontinue Avastin|
|Hemorrhage||Grade 3 or 4||Discontinue Avastin|
|Recent history of hemoptysis of ½ teaspoon (2.5 mL) or more||Withhold Avastin|
|Thromboembolic events|| ||Discontinue Avastin|
|Hypertension, severe||Withhold Avastin if not controlled with medical management; resume once controlled|
|Posterior reversible encephalopathy syndrome (PRES)||Any||Discontinue Avastin|
|Renal toxicity and proteinuria||Nephrotic syndrome||Discontinue Avastin|
|Proteinuria greater than or equal to 2 grams per 24 hours in
absence of nephrotic syndrome ||Withhold Avastin
until proteinuria less than 2 grams per 24 hours |
|Infusion-related reaction||Severe||Discontinue Avastin|
|Clinically significant||Interrupt infusion; resume at a decreased rate of infusion after symptoms resolve|
|Mild, clinically insignificant||Decrease infusion rate|
|Congestive heart failure||Any||Discontinue Avastin|
Select NCCN Guidelines
Bevacizumab plus PC is a standard of care for first-line nsNSCLC
Bevacizumab plus PC holds an NCCN category 1 recommendation per NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.5.2019
|NCCN Guidelines® include bevacizumab plus PC as a treatment option for first-line nsNSCLC patients using the following criteria|
ECOG PS=Eastern Cooperative Oncology Group performance status.
Bevacizumab has an NCCN category 1 recommendation for continuation maintenance† (based on high-level evidence and uniform consensus)
|NCCN Guidelines®|| |
Bevacizumab should be given until progression.
Bevacizumab should not be given as a single agent, unless as maintenance if initially used with chemotherapy.
†Maintenance therapy, as defined by the NCCN.
|Continuation maintenance|| |
Use of at least 1 of the agents given in first line, beyond 4–6 cycles, in the absence of disease progression.
Use of bevacizumab (Avastin) in the first line increases availability of second-line therapeutic options in the treatment of nsNSCLC
In nsNSCLC, Avastin’s approval is only in first line and as treatment to progression or unacceptable toxicity
Adapted with permission from the NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer
V.5.2019. ©2019 National Comprehensive Cancer Network, Inc. The
National Comprehensive Cancer Network makes no warranties of any kind
whatsoever regarding their content, use or application and disclaims
any responsibility for their application in any way. All rights
reserved. The NCCN Guidelines® and illustrations herein may
not be reproduced in any form for any purpose without the express
written permission of NCCN. To view the most recent and complete
version of the NCCN Guidelines, go online to NCCN.org. The NCCN
Guidelines are a work in progress that may be refined as often as new
significant data becomes available.
‡Chemotherapy given for up to 6 cycles.[1,8]
§PS 0–1 non-squamous NSCLC and no recent history of hemoptysis. Bevacizumab should not be given as a single agent unless as maintenance if initially used with chemotherapy. Any regimen with a high risk of thrombocytopenia and the potential risk of bleeding should be used with caution in combination with bevacizumab.