Skin Rash Actually Signifies Better Outcomes for Pancreatic and Lung Cancer Patients
PHILADELPHIA, July 3, 2007-- – The appearance of a
rash in cancer patients treated with erlotinib (Tarceva) is
strongly associated with longer survival, according to researchers
from the drug’s developer, OSI Pharmaceuticals, Inc. This is
not the first time that rash has been associated with a survival
advantage with EGFR inhibitors – a class of drugs which
includes erlotinib, cetuximab, panitumumab and others designed to
block overproduction of the epidermal growth factor receptor
– but it is the most detailed analysis to
date.
The study, published in the July 1 issue of Clinical Cancer
Research, a journal of the American Association for Cancer
Research, reports that for patients taking Tarceva who developed a
moderate to severe rash, survival without progression of disease
was 245 percent longer than in patients who had a mild rash or none
at all. In fact, in the majority of cases, the more severe the
rash, the longer a patient’s cancer was held in check,
researchers found.
This rash, which often looks like acne, can be unpleasant enough
for some people to consider discontinuing treatment, but “it
is important for physicians and patients to understand that this a
positive event because it means there is likely to be a better
clinical outcome,” said the lead author, Bret Wacker, MS
Director of Biostatistics at OSI Pharmaceuticals, Inc.
“Further studies are needed to both identify patients most
likely to develop rash and to determine if dose escalation to
induce rash can improve efficacy.”
Although few patients dropped out of the large Phase III
clinical trials testing Tarceva in advanced non-small cell lung
cancer and pancreatic cancer due to the rash, Wacker said he fears
those who are taking Tarceva outside of a clinical trial may be
likely to stop treatment.
“Some patients are stopping treatment because of the rash,
yet those are the ones who are most likely to benefit,”
Wacker said. “This is a critical problem and rather than
permanently discontinue treatment, patients should talk to their
doctor about an effective and proactive strategy to manage the rash
while continuing Tarceva therapy.”
According to the researchers, these rashes can be controlled
with mild steroids or antibiotics, and in most cases, they will
improve with treatment. They are believed to be due to an
inflammatory response as a result of EGFR inhibition in skin
tissue, Wacker said.
The analysis looked at two placebo-controlled, double-blind,
randomized, Phase III clinical trials testing Tarceva in advanced
non-small cell lung cancer and pancreatic cancer ? studies which
led to approval of the agent for treating both cancers. Wacker and
his team excluded patients who died in the first month after
starting the study because they may not have had time to develop
the rash or the rash may have been under-reported in these ill
patients.
Of the 673 patients in the lung cancer study, called BR.21, and
in the Tarceva-treated group, 81 percent developed a rash, the
majority of which was grade 2 (The study graded rashes from 1,
relatively mild, to 4, severe). The researchers found that the
presence of any rash correlated with overall and progression-free
survival and that these correlations increased with the grade of
rash. Specifically, Tarceva-treated patients who did not develop a
rash survived a median of 3.3 months, compared to 7.1 months for
those with a grade 1 rash, and 11.1 months for patients with more
severe, grade 2 rashes.
They also found, however, that 18 percent of patients treated
with a placebo also developed a rash, and that overall survival in
these patients was also significantly longer (a median of 8.2
months compared to 4.7 months), compared to placebo patients who
didn’t develop a rash. “We don’t know why some
patients treated with a placebo developed a rash, but it could be
due to the strength of their immune system, and that is why they
survived longer,” Wacker said.
In the second clinical trial (known as PA.3) that tested Tarceva
and the chemotherapy drug gemcitabine against a placebo drug and
gemcitabine in 521 patients with advanced pancreatic cancer, 71
percent of patients using Tarceva/gemcitabine developed a rash,
compared with 30 percent of patients in the placebo
group.
This increased rate of rashes in the placebo group makes some
sense, Wacker said, because rashes are known to occur with use of
gemcitabine chemotherapy. But, unlike the BR.21 study, these
pancreatic cancer patients with rashes in the placebo group did not
experience an increase in survival compared to placebo group
patients without a rash.
In the Tarceva treatment group, only a more severe rash of grade
2 or higher was associated with increased survival. Patients with a
grade 2 rash survived a median of 10.8 months, compared to treated
patients with no rash (5.4 months) or a grade 1 rash (5.7 months).
“These different results may be associated with the addition
of gemcitabine with Tarceva, or the lower dose of Tarceva in this
study, but we just don’t know,” he said.
Wacker points out that lack of a rash doesn’t necessarily
mean that patients will not benefit from Tarceva. “A small
percentage of patients who didn’t develop a rash still had
relatively long survival,” he said. “But, still,
overall, patients who don’t develop a rash don’t do as
well as those who do.”
The study was funded by OSI Pharmaceuticals, Inc.
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