CHICAGOGefitinib (Iressa) produced clinically
meaningful improvement in disease-related symptoms in advanced non-small-cell
lung cancer (NSCLC), David F. Cella, PhD, reported at the 39th Annual Meeting
of the American Society of Clinical Oncology (abstract 2531). Dr. Cella is
professor, Northwestern University, and director, Center on Outcomes, Research
and Education (CORE), Evanston Northwestern Health-care, Evanston, Illinois.
The study was supported by AstraZeneca.
The researchers studied symptom improvement in the Iressa
Dose Evaluation in Advanced Lung Cancer (IDEAL 2) trial, which included 216
symptomatic patients with locally advanced or metastatic NSCLC who had more
than two prior chemotherapy regimens containing platinum and docetaxel (Taxotere)
(given separately or concurrently). Patients received 250 or 500 mg/d of oral
Disease-related symptoms were assessed weekly by the Lung
Cancer Subscale (LCS) of the FACT-L questionnaire. The LCS includes seven items
(cough, shortness of breath, tightness in chest, breathing difficulty, appetite
loss, weight loss, and unclear thinking), and the maximum attainable
(asymptomatic) score on the FACT-L is 28.
LCS response was defined as a 2 point or greater improvement
in LCS score sustained for at least 4 weeks with no worsening at any interim
weekly time point. "A group-average change in LCS score of 2 to 3 points
was considered to be clinically meaningful and correlated with differences in
weight loss, performance status, primary disease symptoms, best response to
treatment, and time to disease progression," Dr. Cella said.
The median baseline LCS scores were 16.7 in the group
receiving 250 mg/d gefitinib and 16 for patients receiving 500 mg/d.
"The overall symptom improvement rate across both doses
was 39%. Symptom improvement was rapid: The median time to symptom improvement
was 9 to 10 days, and the median duration was more than 7 months in the 250
mg/d group and 5.4 months in the 500 mg/d group," Dr. Cella reported.
Similar symptom improvement rates were seen when the 2-point
criterion for symptom improvement was increased to 3 points. "Even
applying a 7-point criterion gave symptom improvement rates of 16.7% and 11.4%
for patients receiving 250 mg/m2/d and 500 mg/m2/d,
respectively," he said.
A correlation between symptom improvement and tumor response
was observed at both gefitinib dose levels, such that most patients who had an
objective tumor response or stable disease showed symptom improvement (P <
Among the patients who survived for more than 8 weeks,
median overall survival was greater for those who had symptom improvement than
for those who did not (11.8 months vs 4.9 months, respectively). Patients who
had symptom improvement but did not have a partial response had median overall
survival of 9.7 months. Patients with stable disease also had longer median
overall survival if they had symptom improvement than if they did not.
"Because it forecasts partial response and overall survival, the
symptom improvement seen with gefitinib is unlikely to be due to a placebo
effect. Symptom improvement information is clinically meaningful and
complementary to a direct antitumor effect in these heavily pretreated patients
with advanced NSCLC," Dr. Cella concluded.