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*, Barbara Ann Burtness, Donna Niedzwiecki, Xing Ye, Kathe Douglas, David H. Ilson, Victoria Meucci Villaflor, Steven J. Cohen, Robert J. Mayer, Alan Venook, Al Bowen Benson, Richard M. Goldberg

*Corresponding author for this work

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 treatmentrelated 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.

Original languageEnglish (US)
Pages (from-to)2736-2742
Number of pages7
JournalJournal of Clinical Oncology
Volume34
Issue number23
DOIs
StatePublished - Aug 10 2016

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Esophagogastric Junction
irinotecan
Cisplatin
Drug Therapy
Epirubicin
Fluorouracil
Neoplasms
Adenocarcinoma
oxaliplatin
Treatment Failure
Disease-Free Survival
Cetuximab
Survival
Leucovorin
Poisons
Therapeutics
Safety

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Enzinger, Peter C. ; Burtness, Barbara Ann ; Niedzwiecki, Donna ; Ye, Xing ; Douglas, Kathe ; Ilson, David H. ; Villaflor, Victoria Meucci ; Cohen, Steven J. ; Mayer, Robert J. ; Venook, Alan ; Benson, Al Bowen ; Goldberg, Richard M. / CALGB 80403 (Alliance)/E1206 : A randomized phase II study of three chemotherapy regimens plus cetuximab in metastatic esophageal and gastroesophageal Junction Cancers. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 23. pp. 2736-2742.
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title = "CALGB 80403 (Alliance)/E1206: A randomized phase II study of three chemotherapy regimens plus cetuximab in metastatic esophageal and gastroesophageal Junction Cancers",
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 treatmentrelated 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.",
author = "Enzinger, {Peter C.} and Burtness, {Barbara Ann} and Donna Niedzwiecki and Xing Ye and Kathe Douglas and Ilson, {David H.} and Villaflor, {Victoria Meucci} and Cohen, {Steven J.} and Mayer, {Robert J.} and Alan Venook and Benson, {Al Bowen} and Goldberg, {Richard M.}",
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CALGB 80403 (Alliance)/E1206 : A randomized phase II study of three chemotherapy regimens plus cetuximab in metastatic esophageal and gastroesophageal Junction Cancers. / Enzinger, Peter C.; Burtness, Barbara Ann; Niedzwiecki, Donna; Ye, Xing; Douglas, Kathe; Ilson, David H.; Villaflor, Victoria Meucci; Cohen, Steven J.; Mayer, Robert J.; Venook, Alan; Benson, Al Bowen; Goldberg, Richard M.

In: Journal of Clinical Oncology, Vol. 34, No. 23, 10.08.2016, p. 2736-2742.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CALGB 80403 (Alliance)/E1206

T2 - A randomized phase II study of three chemotherapy regimens plus cetuximab in metastatic esophageal and gastroesophageal Junction Cancers

AU - Enzinger, Peter C.

AU - Burtness, Barbara Ann

AU - Niedzwiecki, Donna

AU - Ye, Xing

AU - Douglas, Kathe

AU - Ilson, David H.

AU - Villaflor, Victoria Meucci

AU - Cohen, Steven J.

AU - Mayer, Robert J.

AU - Venook, Alan

AU - Benson, Al Bowen

AU - Goldberg, Richard M.

PY - 2016/8/10

Y1 - 2016/8/10

N2 - 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 treatmentrelated 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.

AB - 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 treatmentrelated 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.

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