NO USE OF GEFITINIB IN HEAD-NECK CANCER 

J Clin Oncol. 2013 Mar 4. [Epub ahead of print]

Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial.

Argiris A, Ghebremichael M, Gilbert J, Lee JW, Sachidanandam K, Kolesar JM, Burtness B, Forastiere AA.

Source

Athanassios Argiris, The University of Texas Health Science Center at San Antonio, San Antonio, TX; Musie Ghebremichael, Ragon Institute of Harvard, Massachusetts Institute of Technology, Massachusetts General Hospital, and Harvard Medical School; Ju-Whei Lee, Dana-Farber Cancer Institute, Boston, MA; Jill Gilbert, Vanderbilt University, Nashville, TN; Kamakshi Sachidanandam, Jill M. Kolesar, University of Wisconsin, Madison, WI; Barbara Burtness, Fox Chase Cancer Center, Philadelphia, PA; Arlene A. Forastiere, Johns Hopkins University, Baltimore, MD.

Abstract

PURPOSEWe hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODSPatients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing.ResultsTwo hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. CONCLUSIONThe addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.