Originally published as JCO Early Release 10.1200/JCO.2008.17.0530 on March 16 2009

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Phase III Study of Gefitinib Compared With Intravenous Methotrexate for Recurrent Squamous Cell Carcinoma of the Head and Neck

From the Charing Cross Hospital, London; AstraZeneca, Macclesfield, Cheshire; AstraZeneca, Charnwood, Leicestershire, United Kingdom; University of Chicago Medical Center, Chicago, IL; University of Colorado Health Sciences Centre at Fitzsimons, Denver, CO; Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; Chulalongkorn University, Bangkok, Thailand; Centre Hospitalier de l'Université de Montréal, Montreal, Canada; Faculty Hospital of St Anne, Brno, Czech Republic; Peter MacCallum Cancer Centre, Melbourne, Australia; and the Cancer Research Centre, Moscow, Russia.

Corresponding author: J. Simon W. Stewart, MD, FRCP, Imperial College Healthcare NHS Trust, London, United Kingdom; e-mail: s.stewart{at}imperial.ac.uk.

Purpose To compare survival in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with gefitinib 250 or 500 mg/day or standard methotrexate.

Patients and Methods Four hundred eighty-six patients with recurrent SCCHN were randomly assigned to oral gefitinib 250 mg/day, gefitinib 500 mg/day, or methotrexate 40 mg/m² intravenously weekly. Primary end point was overall survival, secondary end points were objective response rate (ORR), safety, symptom improvement, and quality of life (QOL). Exploratory end points included association of efficacy with epidermal growth factor receptor gene copy number and other biomarkers.

Results Neither gefitinib 250 nor 500 mg/day improved overall survival compared with methotrexate (hazard ratio [HR], 1.22; 95% CI, 0.95 to 1.57; P = .12; and HR, 1.12; 95% CI, 0.87 to 1.43; P = .39, respectively). In the gefitinib 250 mg/day, 500 mg/day, and methotrexate groups, respectively, median overall survival was 5.6, 6.0, and 6.7 months; ORRs (Response Evaluation Criteria in Solid Tumors) were 2.7%, 7.6% and 3.9%, with no statistically significant difference between either gefitinib arm and methotrexate. No unexpected adverse events were observed, except for tumor hemorrhage-type events with gefitinib (8.9%, gefitinib 250 mg/day; 11.4%, gefitinib 500 mg/day; 1.9%, methotrexate). QOL improvement rates (Functional Assessment of Cancer Therapy-Head & Neck total score) were 13.4%, 18.0%, and 6.0% for gefitinib 250 mg/day, 500 mg/day, and methotrexate, respectively.

Conclusion In patients with recurrent or metastatic SCCHN, while responses with gefitinib were seen, neither gefitinib 250 nor 500 mg/day improved overall survival compared with methotrexate. With the exception of tumor hemorrhage–type events with gefitinib, the adverse event profiles were generally consistent with those previously observed.

Supported by AstraZeneca.

Presented in part at the 98th Annual Meeting of the American Association for Cancer Research, April 14-18, 2007, Los Angeles, CA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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