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Clinical Trial
. 2016 Aug 10;34(23):2736-42.
doi: 10.1200/JCO.2015.65.5092. Epub 2016 Jul 5.

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

Peter C Enzinger  1 , Barbara Ann Burtness  2 , Donna Niedzwiecki  2 , Xing Ye  2 , Kathe Douglas  2 , David H Ilson  2 , Victoria Meucci Villaflor  2 , Steven J Cohen  2 , Robert J Mayer  2 , Alan Venook  2 , Al Bowen Benson 3rd  2 , Richard M Goldberg  2
Affiliations
Clinical Trial

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

Peter C Enzinger et al. J Clin Oncol. .

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.

Trial registration: ClinicalTrials.gov NCT00381706.

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Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram. ECF-C, epirubicin, cisplatin, and fluorouracil plus cetuximab; FOLFOX-C, oxaliplatin, leucovorin, and fluorouracil plus cetuximab; IC-C, irinotecan and cisplatin plus cetuximab; OS, overall survival; TTF, time to treatment failure.
Fig 2.
Fig 2.
Overall survival for patients with adenocarcinoma by treatment arm. ECF-C, epirubicin, cisplatin, and fluorouracil plus cetuximab; FOLFOX-C, oxaliplatin, leucovorin, and fluorouracil plus cetuximab; IC-C, irinotecan and cisplatin plus cetuximab.
Fig 3.
Fig 3.
Progression-free survival for patients with adenocarcinoma by treatment arm. ECF-C, epirubicin, cisplatin, and fluorouracil plus cetuximab; FOLFOX-C, oxaliplatin, leucovorin, and fluorouracil plus cetuximab; IC-C, irinotecan and cisplatin plus cetuximab.
Fig 4.
Fig 4.
Time to treatment failure for patients with adenocarcinoma by treatment arm. ECF-C, epirubicin, cisplatin, and fluorouracil plus cetuximab; FOLFOX-C, oxaliplatin, leucovorin, and fluorouracil plus cetuximab; IC-C, irinotecan and cisplatin plus cetuximab.
Fig A1.
Fig A1.
Median percentage of expected dose administered for each regimen by cycle. Cycles with fewer than 10 patients were truncated. (A) Epirubicin, cisplatin, and fluorouracil plus cetuximab; (B) irinotecan and cisplatin plus cetuximab; (C) Oxaliplatin, leucovorin, and fluorouracil plus cetuximab.
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