Cetuximab as second-line therapy in patients with metastatic esophageal cancer: A phase II Southwest Oncology Group Study

Abstract

4536 Background: Survival for patients (pts) with metastatic esophageal cancer is poor, with no established therapy for patients failing first-line treatment. Esophageal adenocarcinoma over-expresses the epidermal growth factor receptor (EGFR), providing the rationale for examining the use of the anti-EGFR monoclonal antibody cetuximab. Methods: This was a multicenter, open-label phase II study of single agent cetuximab in pts with metastatic esophageal adenocarcinoma who had failed one prior chemotherapy regimen for advanced disease. Prior (neo) adjuvant therapy was allowed, but prior treatment targeting the EGFR pathway was not. Adequate organ function and Zubrod performance status of 0–2 were required. Pts received cetuximab 400 mg/m2 IV on week one, and 250 mg/m2 IV weekly thereafter. Pts were evaluated for toxicity weekly and for response every 8 weeks. The primary endpoint was a six-month overall survival rate > 40%. Secondary endpoints included progression-free survival, response rate, and toxicity. Tumor tissue was collected for correlative studies. Results: 63 pts were registered, 8 were not eligible. 55 eligible pts (male=49, female=6), median age 61.2 years (range 30.7–88.5) were enrolled. Out of 55 eligible and evaluable pts, 20 survived > 6 months for a 6-month overall survival rate of 36% (95% CI: 24%, 50%). The median overall survival was 4 months (95% CI: 3.2, 5.9), and the median progression-free survival was 1.8 months (95% CI: 1.7, 1.9). There were 3 unconfirmed partial responses. Two pts experienced Grade 4 fatigue, and there was one treatment-related death due to pneumonitis. Four pts had Grade 3 rash, and three of them survived > 6 months. Conclusions: This trial did not meet the primary objective of 23 pts surviving beyond 6 months, and thus cetuximab alone cannot be recommended in the second-line treatment of metastatic esophageal cancer. However, the regimen was associated with a 36% 6-month survival rate, and it was well tolerated. Trials combining cetuximab with cytotoxic chemotherapy in metastatic esophageal cancer are reasonable, and several are in development. Correlative science data from S0415 will be available in June. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone