Cetuximab (C225) plus irinotecan/cisplatin (CPT/Cis) for CPT/Cis-refractory esophageal cancer

Abstract

15580 Background: In esophageal cancer, weekly CPT/Cis is an active regimen, with a response rate (RR) of 57% and time-to- progression (TTP) of 4.2 months (JCO 17:3270;1999). Epidermal growth factor receptor (EGFR) is overexpressed in 30–90% of esophageal tumors and is associated with advanced stage, chemotherapy resistance and poor prognosis. In colon cancer (CA), adding C225, an anti-EGFR monoclonal antibody, to CPT for CPT-refractory patients (Pts) increases RR and TTP (NEJM 351: 337;2004). Methods: Pts with metastatic esophageal/gastroesophageal junction CA who progressed by RECIST criteria on prior CPT/Cis within 3 months of enrollment were eligible. Up to a total of 2 prior regimens were allowed, including interim therapy between progression on prior CPT/Cis and enrollment. CPT/Cis was continued at the prior dose to a maximum of CPT 65 mg/m2/Cis 30 mg/m2 weekly 2 of 3 weeks. C225 was added at 400 mg/m2 week 1, then 250 mg/m2 weekly. Tumor tissue was tested for EGFR overexpression by immunohistochemistry (IHC). Results: 8 Pts were enrolled. 6 male (75%), 2 (25%) female, median age 53, median Karnofsky performance status 80%, 7 adenocarcinoma (adenoCA), 1 squamous cell (SCC). 6 of 8 Pts were EGFR positive (2 1+/ 2 2+/2 3+ by IHC). Median TTP on prior CPT/Cis was 4.4 months (range, 1.8 to 14.4 months). 1 confirmed partial response (PR) was seen in a Pt with adenoCA (EGFR 3+). 2 Pts had stable disease (SD) and 5 had progressive disease (PD). 1 Pt with SD for 2.9 months had SCC (EGFR 2+) while the other with SD for 3.7 months had adenoCA (EGFR negative). Significant grade 3/4 toxicities included lymphopenia (4 Pts, all grade 3), neutropenia (1 Pt, grade 4), hypomagnesemia (1 Pt, grade 3). Rash was manageable, with 4 Pts with grade 1 and 3 Pts with grade 2 skin toxicity. 1 Pt died of non-neutropenic sepsis from PD after 3 weeks of therapy (this Pt was off treatment for 3–4 weeks prior to death). Conclusions: Adding C225 to CPT/Cis for CPT/Cis-refractory esophageal cancer is well-tolerated; 1 PR has been observed to date. Accrual is ongoing to 25 Pts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech, Pfizer, sanofi-aventis