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Clinical Trial
. 2013 Apr 10;31(11):1405-14.
doi: 10.1200/JCO.2012.45.4272. Epub 2013 Mar 4.

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

Athanassios Argiris  1 , Musie Ghebremichael, Jill Gilbert, Ju-Whei Lee, Kamakshi Sachidanandam, Jill M Kolesar, Barbara Burtness, Arlene A Forastiere
Affiliations
Clinical Trial

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

Athanassios Argiris et al. J Clin Oncol. .

Abstract

Purpose: We 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 methods: Patients 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.

Results: Two 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.

Conclusion: The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.

Trial registration: ClinicalTrials.gov NCT00088907.

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Conflict of interest statement

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

Figures

Fig 1.
Fig 1.
CONSORT diagram representing enrollment and outcomes of patients in the docetaxel/placebo (arm A) or docetaxel/gefitinib (arm B) treatment group. RECIST, Response Evaluation Criteria in Solid Tumors.
Fig 2.
Fig 2.
Kaplan-Meier estimates of (A) overall survival by treatment arm (n = 239) and (B) time-to-progression by treatment arm (n = 239). Cens, censored.
Fig 3.
Fig 3.
Forest plot representing hazard ratios (HRs) with 95% CIs of overall survival in patient subgroups. Cav, cavity; CT, chemotherapy; LCL, lower confidence limit; Med A, median overall survival in arm A; Med B, median overall survival in arm B; PS, performance status; RT, radiotherapy; UCL, upper confidence limit.
Fig 4.
Fig 4.
Kaplan-Meier estimates of overall survival by treatment arm for (A) patients ≥ 65 years (n = 83) and (B) patients younger than 65 years (n = 156). Cens, censored.
See this image and copyright information in PMC

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