A Phase III randomized parallel-group study of gefitinib (IRESSA) versus methotrexate (IMEX) in patients with recurrent squamous cell carcinoma of the head and neck

Abstract

3522 Background: In Phase I and II studies, gefitinib (IRESSA) has demonstrated evidence of anti-tumor activity in patients with head and neck cancer. This multi-center, randomized, partially-blinded, parallel-group, comparative Phase III trial (IMEX: IRESSA vs MEthotreXate) investigated gefitinib versus methotrexate in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN). Methods: Patients with histologically-confirmed recurrent SCCHN were randomized (1:1:1) to gefitinib 250 mg/day, gefitinib 500 mg/day or methotrexate 40 mg/m2 weekly (with the option to escalate to a maximum of 60 mg/m2 in the absence of unacceptable toxicity). Gefitinib doses were blinded. The primary endpoint was overall survival. Secondary endpoints were objective response rate (ORR, assessed by the treating physician by RECIST), safety and tolerability, symptom improvement and quality-of-life (assessed using the Functional Assessment of Cancer Therapy-Head & Neck [FACT-HN P=0.12] and HR 1.12 [95% CI 0.87 - 1.43; P=0.39], respectively). Median overall survival times in the 3 groups were 5.6 (gefitinib 250 mg/day), 6.0 (gefitinib 500 mg/day) and 6.7 (methotrexate) months. ORRs were 2.7%, 7.6% and 3.9% in the gefitinib 250 mg/day, 500 mg/day and methotrexate groups, respectively, with no statistically significant difference between each of the gefitinib arms and methotrexate. Adverse events were consistent with those previously observed for gefitinib and methotrexate with the exception of tumor hemorrhage, which was observed in: 8.9% (14/158), 11.4% (19/166), and 1.9% (3/159) in the gefitinib 250 mg/day, 500 mg/day and methotrexate groups, respectively. Conclusions: Neither gefitinib (IRESSA) 250 mg/day nor 500 mg/day demonstrated improvement in overall survival compared to methotrexate. With the exception of tumor hemorrhage with gefitinib, the adverse event profiles were generally consistent with those previously observed for each agent. IRESSA is a trademark of the AstraZeneca group of companies