SEOUL, South Korea -- Targeted therapy with the receptor tyrosine kinase inhibitor gefitinib (Iressa) demonstrated noninferiority to docetaxel (Taxotere) in treatment of non-small-cell lung cancer in a large multicenter trial.
SEOUL, South Korea, Sept. 5 -- Targeted therapy with the receptor tyrosine kinase inhibitor gefitinib (Iressa) demonstrated noninferiority to docetaxel (Taxotere) in treatment of non-small-cell lung cancer in a large multicenter trial.
Patients treated with gefitinib had a median overall survival of 7.6 months and a one-year survival of 32%, which did not differ from results with docetaxel, Jean-Yves Douillard, M.D., of Rene Gauducheau Medical Oncology Center in Nantes, reported here at the International Association for the Study of Lung Cancer's world conference.
The epidermal growth factor receptor antagonist demonstrated better tolerability compared with docetaxel, and significantly more gefitinib-treated patients had clinically meaningful improvement in quality of life, Dr. Douillard and colleagues found.
In a discussion that followed Dr. Douillard's presentation, Frances Shepherd, M.D., of Princess Margaret Hospital in Toronto, concluded that "EGRF tyrosine kinase inhibitor therapy is a reasonable option for the second-line treatment of non-small-cell lung cancer."
The Phase III trial involved 1,466 patients from 149 centers in 24 countries. All the patients had progressive or recurrent disease following initial chemotherapy and were considered candidates for additional chemotherapy with docetaxel. Eligible patients had received no more than two prior regimens, one of which had to be a platinum-based regimen, said Dr. Douillard.
The patients were randomized to gefitinib 250 mg a day orally or docetaxel 75 mg/m2 intravenously every three weeks. The primary endpoint was overall survival. Additionally, coprimary analyses of noninferiority were performed in all patients and superiority in patients with high EGFR gene expression.
Secondary endpoints consisted of progression-free survival, objective response rate, quality of life, disease-related symptoms, and safety and tolerability.
At the end of the study, docetaxel-treated patients had a median overall survival of eight months and a one-year survival of 34%. Neither outcome differed significantly from the gefitinib group. Overall response rates were 9.1% with gefitinib and 7.6% with docetaxel.
Patients with elevated EGFR gene expression had a median overall survival of 8.4 months and one-year survival of 32% with gefitinib, compared with 7.5 months and 35% in the docetaxel group. The differences were not statistically significant, said Dr. Douillard.
Extensive pre-planned subgroup analyses revealed only one significant difference between treatment groups. Patients who had received two prior chemotherapy regimens fared better with docetaxel (P=0.031).
With respect to tolerability, grade 3-4 hematologic adverse events occurred in no more than 2.2% of gefitinib patients. By comparison, docetaxel-treated patients had a 58.2% incidence of grade 3-4 neutropenia and a 42.3% incidence of grade 3-4 leukopenia.
Among nonhematologic adverse events (all grades), rash and diarrhea were more common in the gefitinib group, whereas docetaxel was associated with more asthenia, nausea, alopecia, and neurotoxicity.
Dr. Douillard reported that 25.1% of gefitinib patients had clinically relevant improvement in quality of life as assessed by the FACT-L questionnaire, compared with 14.7% of docetaxel patients (P