Lung Cancer: Avastin Efficacy Data

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.

Study E4599 Results: Avastin plus PC demonstrated superior survival to PC alone in first-line advanced nsNSCLC

In Study E4599, median OS with Avastin plus PC was 12.3 months vs 10.3 months with PC alone (HR=0.80 [95% CI, 0.68–0.94], P=0.013)[1,8]

nsNSCLC=non-squamous non-small cell lung cancer; PC=paclitaxel + carboplatin; OS=overall survival; HR=hazard ratio; CI=confidence interval.

More than half of Avastin-treated patients were alive at 1 year in Study E4599.[8]

  • Median progression-free survival (PFS) with Avastin plus PC was 6.2 months vs 4.5 months with PC alone (HR=0.66 [95% CI, 0.57–0.77), P<0.001), based on investigator assessment (not independently verified)[1,8]
  • Response rate with Avastin plus PC was 35% vs 15% with PC alone (P<0.001), based on investigator assessment (not independently verified)[8]

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

Study E4599: OS in the intent-to-treat population[1,8]

Study E4599 was the first prospective Phase III randomized clinical trial of an FDA-approved biologic in first-line advanced non-squamous NSCLC to demonstrate statistically significant improvement in OS (>12 months), its primary endpoint, in an intent-to-treat population.[1,8]

The intent-to-treat population included all patients randomized before start of treatment. The results of Study E4599 included both progressors and non-progressors.[8]

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

In nsNSCLC, approval of Avastin 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

Study E4599 was a large Phase III trial that investigated a broad range of over 850 patients with advanced nsNSCLC[8,10,11]

Patients studied in ECOG Study E4599 included:
  • First-line, locally advanced, metastatic or recurrent NSCLC
  • All predominantly non-squamous histologies
    • Adenocarcinoma
    • Large cell tumors
    • Bronchioloalveolar carcinoma
    • Undifferentiated NSCLC, not otherwise specified
  • Centrally located tumors
  • ECOG PS 0–1

ECOG=Eastern Cooperative Oncology Group.

  • Study E4599 was a Phase III, randomized, active-controlled, open-label, multicenter study that compared Avastin plus PC versus PC alone in patients with locally advanced, metastatic, or recurrent nsNSCLC[1,8]

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

Histologies in Study E4599[3,8,11]

One patient in the Avastin plus PC arm was missing in the evaluation of histologies.
 

The intent-to-treat population included all patients randomized before start of treatment. The results of Study E4599 included both progressors and non-progressors. Baseline demographics and patient characteristics were evaluated for the intent-to-treat population. Histology information was not available for 1 patient in the Avastin + PC arm.[3,8,11]
 

 

The WARNINGS AND PRECAUTIONS section of the Avastin full Prescribing Information states:
In clinical studies in NSCLC where patients with CNS metastases who completed radiation and surgery more than 4 weeks prior to the start of Avastin were evaluated with serial CNS imaging, symptomatic grade 2 CNS hemorrhage was documented in 1 of 83 Avastin-treated patients (rate 1.2%; 95% CI, 0.06%–5.93%). 1

CNS=central nervous system.