Bevacizumab Combined With Chemotherapy Prolongs Survival for Some Patients with Advanced Lung Cancer
Preliminary results from a large, randomized clinical trial for
patients with previously untreated advanced non-squamous, non-small
cell lung cancer show that those patients who received bevacizumab
(Avastin) in combination with standard chemotherapy lived
longer than patients who received the same chemotherapy without
The clinical trial was sponsored by the National Cancer Institute
(NCI), part of the National Institutes of Health, and conducted
by a network of researchers led by the Eastern Cooperative Oncology
Group. Genentech, Inc., South San Francisco, Calif., which manufactures
bevacizumab, provided bevacizumab for the trial under the Cooperative
Research and Development Agreement (CRADA) with NCI for the clinical
development of bevacizumab.
The Data Monitoring Committee overseeing the trial (known as
E4599)* recommended that the results of a recent interim analysis
public because the study had met its primary endpoint of improving
overall survival. Researchers found that patients in the study
who received bevacizumab in combination with standard chemotherapy
(a treatment regimen of paclitaxel and carboplatin) had a median
overall survival of 12.5 months compared to patients treated with
the standard chemotherapy alone, who had a median survival of 10.2
months. This difference is statistically significant. Detailed
results from this trial will be presented at the American Society
of Clinical Oncology Annual Meeting (ASCO) to be held in Orlando,
Fla., on May 13-17, 2005.
“The exciting results of this randomized study reveal, for the first
time, an improvement in survival with the addition of a targeted
agent to standard chemotherapy in this patient population," said
Study Chair Alan B. Sandler, M.D., of the Vanderbilt University
Medical Center in Nashville, Tenn.
“This study demonstrates that mechanistic-based interventions such
as angiogenesis inhibitors are making important contributions in
improving cancer outcomes,” said NCI Director Andrew C. von
Eschenbach, M.D. “In combination with standard therapies,
they can be used for a variety of cancers, leading to increased
A total of 878 patients with advanced non-squamous, non-small cell
lung cancer (NSCLC) who had not previously received systemic chemotherapy
were enrolled in this study between July 2001 and April 2004. Patients
were randomized to one of the two treatment arms. One patient group
received standard treatment six cycles of paclitaxel and carboplatin.
The second group received the same six-cycle chemotherapy regimen
with the addition of bevacizumab, followed by bevacizumab alone
until disease progression.
Patients with squamous cell carcinoma of the lung were not included
in the study because previous clinical experience suggested that
patients with this particular type of NSCLC had a higher risk of
serious bleeding from the lung after bevacizumab therapy. Patients
with a prior history of frank hemoptysis (coughing up blood) were
also not enrolled on the trial.
The most significant adverse event observed in this study was life-threatening
or fatal bleeding, primarily from the lungs. This occurred infrequently,
but was more common in the patient group that received bevacizumab
in combination with chemotherapy than in the patient group that
received only chemotherapy. A full description of side effects
observed in this trial will be presented at the ASCO Annual Meeting
in May, as well.
Bevacizumab, a humanized monoclonal antibody**, is designed to
bind to and inhibit vascular endothelial growth factor (VEGF).
VEGF is a protein that plays a critical role in tumor angiogenesis,
the formation of new blood vessels to the tumor.
“This trial represents another step in a series of recent important
advances in treatment for patients with advanced lung cancer,” said
James H. Doroshow, M.D., director of NCI’s Division of Cancer
Treatment and Diagnosis and leader of NCI’s Clinical Trials
Working Group. “Important progress continues to be made by
targeting molecular pathways critical to the growth and survival
of cancer cells. It is through better understanding of these molecular
processes that significant advances will be made in the treatment
of this disease.”
An estimated 172,570 people will be diagnosed with lung cancer
in the United States in 2005. Lung cancer is the second most commonly
diagnosed cancer and the leading cause of cancer-related death
in both men and women in this country. An estimated 163,510 deaths
from lung cancer will occur in 2005 in the United States, accounting
for about 29 percent of all cancer-related deaths in the nation.
For more information about cancer, visit the NCI Web site at
http://www.cancer.gov or call NCI's Cancer Information Service
at 1-800-4 CANCER (1-800-422-6237).
* E4599: A randomized phase II/III trial
of paclitaxel plus carboplatin with or without bevacizumab in patients
with advanced non-squamous non-small cell lung cancer.
** Monoclonal antibodies are laboratory-produced
substances that can locate and bind to specific
substances in the body. “Humanized” monoclonal antibodies
include some sequences that are the same as those in human antibodies
in order to avoid being destroyed by the patient’s own immune system.