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[1]:

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.[1]

  • 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[1]

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage

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.[1]

Survival benefits were seen with Avastin when continued until disease progression or unacceptable toxicity[1]

  • The OS results seen in Study E4599 were achieved with Avastin given until disease progression or unacceptable toxicity[1]
  • 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[12]
  • In Study E4599, patients in the Avastin plus PC arm received an average of 8.9 cycles of study treatment[3]
    • Study treatment consisted of either Avastin plus PC or Avastin alone after PC was discontinued

Important treatment considerations—dose modifications[1]

No dose reductions for Avastin are recommended.

Dose modifications for adverse reactions

Adverse reaction Severity  Dose modification
Gastrointestinal perforation and fistulae
  • Gastrointestinal perforation, any grade
  • Tracheoesophageal fistula, any grade
  • Fistula, grade 4
  • Fistula formation involving any internal organ
Discontinue Avastin
Wound healing complications
  • Wound healing complications requiring medical intervention
  • Necrotizing fasciitis
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
  • Arterial thromboembolism, severe
  • Venous thromboembolism, grade 4
Discontinue Avastin
Hypertension
  • Hypertensive crisis
  • Hypertensive encephalopathy
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 ≥2 g/24 h in absence of nephrotic syndrome Withhold Avastin until proteinuria <2 g/24 h
Infusion reaction Severe infusion reaction 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

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage

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.6.2018[9]

NCCN Guidelines® include bevacizumab plus PC as a treatment option for first-line nsNSCLC patients using the following criteria
  • No history of hemoptysis
  • ECOG PS 0–1

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)[9]

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.

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage

Treatment algorithm

Use of bevacizumab (Avastin) in the first line increases availability of second-line therapeutic options in the treatment of nsNSCLC[9]

In nsNSCLC, Avastin’s approval is only in first line and as treatment to progression or unacceptable toxicity[1]

Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.6.2018. ©2018 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.[9]
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.[9]

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage