Adding cetuximab (Erbitux) to a standard
chemotherapy regimen of cisplatin
and vinorelbine (Navelbine) was
safe and produced "promising activity"
against non-small-cell lung cancer
(NSCLC) in interim phase II results
from the Lung Cancer Cetuximab
Investigator Ulrich Gatzemeier,
MD, of Grosshansdorf Hospital in
Hamburg reported an overall response
rate of 53.3% among 30 patients given
the standard regimen plus cetuximab
vs 32.3% for 31 patients given only the
standard regimen (ASCO abstract
2582). The cetuximab arm included 1
complete responder and 15 partial
responders. No complete responses
and 10 partial responses were recorded
in the standard therapy arm
(see Table 1).
Conversely, progressive disease was
more than three times higher for patients
receiving standard therapy without
cetuximab. Seven patients (22.6%)
in the standard therapy arm had progressive
disease vs two patients (6.7%)
in the cetuximab arm. Stable disease
was also slightly higher in the standard
therapy arm, 14 patients (45.2%),
compared to 12 (40%) in the cetuximab
"We hope that we can increase the
response rate with the addition of
cetuximab to a two-drug combination,"
Dr. Gatzemeier told ONI.
Until now, phase III trials adding a
third drug to the standard cisplatin/
vinorelbine combination have failed
to boost response rates for NSCLC
beyond 26% to 30% or extend the
median time to progression beyond 4
months. The LUCAS study did not
report data on duration of response or
time to progression.
Dr. Gatzemeier cautioned that data
reported are only interim. The trial
opened enrollment early in 2002, and
accrual of 40 patients in each arm is
complete, he said, forecasting final
results would be ready by the end of
Researchers at hospitals in Spain,
Poland, and France and at Merck KgaA
in Darmstadt, Germany, are collaborating
in the study. Merck licenses
cetuximab from ImClone Systems,
Inc., a US-based biotechnology company.
Synergy in Lab Models
A monoclonal antibody, cetuximab
targets the HER1/epidermal growth
factor receptor (HER1/EGFR), which
is highly expressed in most advanced
cases of NSCLC. It has shown synergistic
activity with cisplatin and vi-
norelbine in laboratory tumor models,
according to the investigators.
Inclusion criteria included diagnosis
of histologically confirmed stage
IIIB or IV NSCLC with documented
malignant pleural effusion, immunohistological
evidence of EGFR-expression
in the primary tumor, and at least
one metastasis and Karnofsky performance
status ≥ 70. Patients with previous
chemotherapy, monoclonal antibody
exposure, or EGFR targeting
therapy were excluded.
All patients received a standard
regimen of 80 mg/m2 of cisplatin and
25 mg/m2 of vinorelbine on days 1 and
8 in 3-week cycles. Half the patients
also received an initial infusion of
400 mg/m2 of cetuximab followed by
250 mg/m2 weekly. Response is assessed
every two cycles by CT scan
No Apparent Toxicity Increase
Although 61% of patients in the
experimental arm had grades 3/4 adverse
events and seven were withdrawn
from the study, the investigators reported
that cetuximab did not appear
to increase chemotherapy toxicity.
Among patients who received the standard
regimen without cetuximab,
69.4% had grades 3/4 adverse events
and four could not continue on study.
The most common adverse events
in both groups were neutropenia followed
by nausea/vomiting. Two patients
on cetuximab experienced rash,
which other researchers have correlated
with response to EGFR-targeting
agents (see Table 2).
"The safety profile at this point is
good, without major increase of toxicity
regarding cytotoxic chemotherapy,"
Dr. Gatzemeier said. "Adverse
events like rash and the relation to
response have to be analyzed."