NEW YORK-Panitumumab, a
100% human high-affinity IgG2 monoclonal
antibody (MoAb) against the
epidermal growth factor receptor
(EGFR), appears effective in the treatment
of colorectal cancer and is well
tolerated, according to Joel Randolph
Hecht, MD, director of the Gastrointestinal
UCLA School of Medicine.
Dr. Hecht presented recent clinical
data on panitumumab in colorectal
cancer at the Chemotherapy Foundation
Symposium XXII. Panitumumab
(formerly known as ABX-EGF, codeveloped
by Amgen, Inc., and Abgenix)
was created using Abgenix's Xeno-
Mouse technology, which, according
to the company, "enables the rapid
generation and selection of high affinity,
fully human antibody product candidates
to a variety of disease targets."
Phase II Monotherapy
Dr. Hecht reviewed his group's ongoing
multicenter phase II trial of panitumumab
monotherapy, which he had
presented at the 2004 ASCO annual
meeting (abstract 3511). In that study,
the monoclonal antibody was found
to have antitumor activity when administered
as a single-agent to 148
patients with metastatic colorectal cancer
who had failed to respond to chemotherapy
with a fluoropyrimidine
with or without leucovorin, and irinotecan
(Camptosar) or oxaliplatin
(Eloxatin) or both.
EGFR expression was determined
by immunohistochemistry. "I personally
do not think EGFR staining means
anything, but at the time the study was
done, we thought it might be significant,"
Panitumumab was given at 2.5 mg/
kg intravenously over 1 hour, once a
week for 8 weeks. "We've now gone
beyond this dosage, but that is how
this trial was done," Dr. Hecht commented.
At least 95% of patients experienced
some form of skin rash, but
only 3% had grade 3 rash, and no
patients had grade 4 rash. Grade 3
fatigue and vomiting were seen in 2%
and 1% of patients, respectively.
Panitumumab was administered
without premedication, with the ex-ception of one patient who experienced
a grade 3 infusion-related event.
"Response rates were very similar
to what has been seen with cetuximab
[Erbitux]," Dr. Hecht told ONI. "The
overall response rate was 10%," with
13 patients having responded at the
time of the first 8-week evaluation,
and two patients responding after the
second 8-week evaluation (both at
week 18). "There was also a reasonable
amount of stable disease," he added,
"but since 48% of patients were
either responders or had stable disease
at the first look, median time to
progression was only about 2 months."
Median overall survival was 7.9
months, and median time to progression
was 2.0 months.
Noting that some striking clinical
responses were seen early in the course
of therapy, he added that "some of
these patients responded clinically
within 1 week." As with trials of cetuximab,
there was no correlation between
the degree of EGFR staining
and response to panitumumab, he
Phase II With IFL
Dr. Hecht also discussed a phase II
trial of panitumumab with irinotecan,
fluorouracil (5-FU), and leucovorin
(IFL, Saltz regimen) in patients with
metastatic colorectal cancer, some results
of which were presented at the
29th ESMO (European Society for
Medical Oncology) Congress by Jordan
Berlin, MD, of Vanderbilt University
Medical Center (abstract 265).
The first part of this multicenter,
open-label, single-arm study included
19 patients who received first-line
therapy with panitumumab and standard
IFL. Panitumumab 2.5 mg/kg
was administered over a 1-hour period
weekly in 6-week courses (on days
1, 8, 15, 22, 29, and 36) immediately
followed by irinotecan 125 mg/m2,
leucovorin 20 mg/m2, and 5-FU
500 mg/m2 on days 1, 8, 15, and 22.
The second part is a trial of first-line
therapy with panitumumab/FOLFIRI
(folinic acid [leucovorin], infusional
5-FU, and irinotecan) in 24 patients.
Data for the first part of the study
showed an unacceptably high incidence
of diarrhea at 84% (grade 3 in
42%) and a 16% incidence of nausea,
abdominal pain, dehydration, and hypokalemia.
Responses, assessed using
RECIST criteria, were comparable to
what has been seen in phase II studies
of IFL alone and of IFL with cetuximab,
"with some stable disease and a
very low incidence of progressive disease,"
Dr. Hecht said.
The overall response rate after
6 weeks of therapy was 47% (42%
partial response, 5% complete response),
with stable disease in 32% of
patients at week 6 or later. Median
progression-free survival time was 8.2