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Predictive Factors for Outcome in a Phase II Study of Gefitinib in Second-Line Treatment of Advanced Esophageal Cancer Patients

Maarten L. Janmaat, Mariëlle I. Gallegos-Ruiz, José A. Rodriguez, Gerrit A. Meijer, Walter L. Vervenne, Dick J. Richel, Cees Van Groeningen, Giuseppe Giaccone

From the Departments of Medical Oncology and Pathology, Vreije Universiteit Medical Center; and Academic Medical Center, Amsterdam, the Netherlands

Address reprint requests to Giuseppe Giaccone, MD, PhD, Department of Medical Oncology, Vreije Universiteit Medical Center, De Boelelaan 1117, PO Box 7057, MB 1007 Amsterdam, the Netherlands; e-mail: g.giaccone{at}vumc.nl

PURPOSE: The efficacy of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib was assessed in a phase II study in patients with advanced esophageal cancer. Several biologic features were investigated as potential markers of gefitinib activity.

PATIENTS AND METHODS: Patients with advanced esophageal cancer, who had failed one line of prior chemotherapy, were administered gefitinib 500 mg/d. Response was evaluated every 8 weeks. Tumor material obtained before gefitinib treatment was investigated for gene mutations in EGFR, k-ras, and PIK3CA; protein expression levels of EGFR, p-Akt, and p-Erk; and EGFR gene amplification.

RESULTS: Of the 36 enrolled patients, one (2.8%) achieved a partial response, 10 (27.8%) had stable disease, 17 (47.2%) experienced progression on treatment, and eight (22.2%) were not assessable for response. The progression-free survival time was 59 days, and the median overall survival time was 164 days. Although EGFR or PIK3CA mutations were absent, k-ras mutations were found in two patients with progressive disease. High EGFR gene copy number was identified in two patients experiencing partial response or progressive disease. A higher disease control rate (response plus stable disease) was observed in females (P = .038) and in patients with squamous cell carcinoma (SCC; P = .013) or high EGFR expression (P = .002).

CONCLUSION: Gefitinib has a modest activity in second-line treatment of advanced esophageal cancer. However, the patient outcome was significantly better in female patients and in patients demonstrating high EGFR expression or SCC histology. The selection of esophageal cancer patients for future studies with EGFR-TKIs based on the level of EGFR expression in their tumors or SCC histology should be considered.

Supported in part by AstraZeneca.

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

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Related Correspondence

• Epidermal Growth Factor Receptor Gene Copy Number in Esophageal Cancer and Outcome Prediction to Gefitinib: Does Intratumoral Heterogeneity Matter?
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  JCO 2006 24: 5465 [Full Text]

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