CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers

Author:

Enzinger Peter C.1,Burtness Barbara Ann1,Niedzwiecki Donna1,Ye Xing1,Douglas Kathe1,Ilson David H.1,Villaflor Victoria Meucci1,Cohen Steven J.1,Mayer Robert J.1,Venook Alan1,Benson Al Bowen1,Goldberg Richard M.1

Affiliation:

1. Peter C. Enzinger and Robert J. Mayer, Dana-Farber Cancer Institute, Harvard Medical School, and Alliance for Clinical Trials in Oncology, Boston, MA; Barbara Ann Burtness and Steven J. Cohen, Fox Chase Cancer Center; Barbara Ann Burtness, Steven J. Cohen, and Al Bowen Benson III, Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group, Philadelphia, PA; Donna Niedzwiecki, Xing Ye, and Kathe Douglas, Alliance Statistics and Data Center, Duke University,...

Abstract

Purpose To determine the optimal chemotherapy backbone for testing in future US cooperative group studies for metastatic esophageal and gastroesophageal junction cancers. Cetuximab was added to each treatment arm based on promising preclinical data. Patients and Methods Patients with previously untreated metastatic esophageal or gastroesophageal junction cancer were randomly assigned at a one-to-one-to-one ratio to epirubicin, cisplatin, and continuous-infusion fluorouracil (ECF), irinotecan plus cisplatin (IC), or FOLFOX (oxaliplatin, leucovorin, and bolus and infusional fluorouracil). All treatment programs included cetuximab once per week. The primary end point was response rate. Secondary outcomes included overall survival, progression-free survival, time to treatment failure, and safety. As prespecified, primary and secondary analyses were conducted only among patients with adenocarcinoma. Results This study randomly assigned 245 patients, including 222 with adenocarcinoma. Among patients with adenocarcinoma, response rate was 60.9% (95% CI, 47.9 to 72.8) for ECF plus cetuximab, 45.0% (95% CI, 33.0 to 57.0) for IC plus cetuximab, and 54.3% (95% CI, 42.0 to 66.2) for FOLFOX plus cetuximab. Median overall survival was 11.6, 8.6, and 11.8 months; median progression-free survival was 7.1, 4.9, and 6.8 months; and median time to treatment failure was 5.6, 4.3, and 6.7 months for each of these arms, respectively. FOLFOX plus cetuximab required fewer treatment modifications compared with ECF plus cetuximab and IC plus cetuximab (P = .013), and fewer patients were removed from treatment because of an adverse event or experienced treatment-related death. Conclusion In combination with cetuximab, ECF and FOLFOX had similar efficacy, but FOLFOX was better tolerated. Although differences were nonsignificant, IC plus cetuximab seemed to be the least effective and most toxic of the three regimens tested.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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