SEATTLE-The largest prospective
trial of patients with bronchoalveolar
carcinoma (BAC) showed that
gefitinib (Iressa) shows single-agent
activity and that women tend to survive
longer on the drug than men.
Howard L. West, MD, of the Swedish
Cancer Institute in Seattle reported
results of the Southwest Oncology
Group (SWOG) study S0126 (abstract
Although considered to be poorly
responsive to conventional chemotherapy,
BAC had not been widely
studied despite the fact that it is becoming
more common, especially
among young, nonsmoking women,
Dr. West noted. "But there were anecdotal
reports of rapid and remarkable
radiographic responses to gefitinib,
some quite long-lasting," he said.
The study included 145 patients
(136 evaluable) with advanced BAC,
including 102 who had no prior chemotherapy.
There was no requirement
that the patients' tumors express the
epithelial growth factor receptor
(EGFR), the drug's target.
The main study objective was to
determine potential clinical, radiographic,
pathologic, and molecular
markers predictive of outcome under
the influence of gefitinib therapy. The
primary study endpoint was overall
survival. Secondary endpoints included
progression-free survival (PFS), the
response rate by RECIST (Response
Evaluation Criteria in Solid Tumors)
criteria, and toxicity. Patients were
treated with daily oral doses of gefitinib
(500 mg) until there was evidence
of progression or prohibitive
Dr. West reported that the response
rates were 19% in previously untreated
patients (including 6% complete
responses) and 9% in previously treated
patients. "The clinical benefit rate
(complete responses, partial responses,
and stable responses) approached
50% in both groups," he said. Median
survival was similar in both groups
(10 to 12 months), as was median PFS
(3 to 4 months).
"There was a subset of patients with
BAC who experienced prolonged survival
with gefitinib. One of the most
important variables was gender. Women
had a median survival of 19 months
compared to 8 months for men," Dr.
West said. "This relationship was
present for both previously treated
and untreated patients."
One year survival was about 50%
in each subgroup. "A small group of
patients continue to have no progression
beyond 1 year," Dr. West said.
Better Survival With Rash
Development of any type of rash
was associated with significantly better
survival, and patients with grade 1
rash had survival similar to those with
grade 2 or 3 rash. "There were no
responses among patients who did not
develop a rash," Dr. West said.
Patients who had never smoked also
had better survival. Median survival of
nonsmokers has not yet been reached.
Toxicity was predominantly an acneiform
rash (82%; 11% grade 3 or 4) and
diarrhea (69%; 20% grade 3, no grade
4). Fifteen patients (11%) came off trial
because of toxicity. Just over one-third
had dose reduction to 250 mg/day.
Pulmonary toxicity has been a concern
with this drug, and there were
three deaths among patients in this
study that were considered to be probably
treatment-related. "In each case,
the patient had a worsening of diffuse
pulmonary infiltrates and had toxemia
of unclear etiology, although it
may represent interstitial lung disease,"
Dr. West told Oncology News