Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147

Jocelin Huang, Suresh G. Nair, Michelle R. Mahoney, Garth D. Nelson, Anthony F. Shields, Emily Chan, Richard M. Goldberg, Sharlene Gill, Morton S. Kahlenberg, James T. Quesenberry, Stephen N Thibodeau, Thomas Christopher Smyrk, Axel F Grothey, Frank A Sinicrope, Thomas A. Webb, Gist H. Farr, Barbara A Pockaj, Jeffrey L. Berenberg, Margaret Mooney, Daniel J. SargentSteven Robert Alberts

Research output: Contribution to journalArticle

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Abstract

Background Two arms with FOLFIRI, with or without cetuximab, were initially included in the randomized phase III intergroup clinical trial NCCTG (North Central Cancer Treatment Group) N0147. When other contemporary trials demonstrated no benefit to using irinotecan as adjuvant therapy, the FOLFIRI-containing arms were discontinued. We report the clinical outcomes for patients randomized to FOLFIRI with or without cetuximab. Patients and Methods After resection, patients were randomized to 12 biweekly cycles of FOLFIRI, with or without cetuximab. KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation status was retrospectively determined in a central lab. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS) and toxicity. Results One hundred and six patients received FOLFIRI and 40 received FOLFIRI plus cetuximab. Median follow-up was 5.95 years (range, 0.1-7.0 years). The addition of cetuximab showed a trend toward improved DFS (hazard ratio [HR], 0.53; 95% CI, 0.26-1.1; P =.09) and OS (HR, 0.45; 95% CI, 0.17-1.16; P =.10) in the overall group, regardless of KRAS status, and in patients with wild type KRAS. Grade ≥ 3 nonhematologic adverse effects were significantly increased in the cetuximab versus FOLFIRI-alone arm (68% vs. 46%; P =.02). Adjuvant FOLFIRI resulted in a 3-year DFS less than that expected for FOLFOX. Conclusion In this small randomized subset of patients with resected stage III colon cancer, the addition of cetuximab to FOLFIRI was associated with a nonsignificant trend toward improved DFS and OS. Nevertheless, considering the limitations of this analysis, FOLFOX without the addition of a biologic agent remains the standard of care for adjuvant therapy in resected stage III colon cancer.

Original languageEnglish (US)
Pages (from-to)100-109
Number of pages10
JournalClinical Colorectal Cancer
Volume13
Issue number2
DOIs
StatePublished - 2014

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Colonic Neoplasms
Disease-Free Survival
Neoplasms
irinotecan
Therapeutics
Survival
Phase III Clinical Trials
Biological Factors
Standard of Care
Cetuximab
Oncogenes
Sarcoma
Randomized Controlled Trials
Mutation

Keywords

  • Adjuvant therapy
  • Disease free survival
  • Overall survival
  • Response rate

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147. / Huang, Jocelin; Nair, Suresh G.; Mahoney, Michelle R.; Nelson, Garth D.; Shields, Anthony F.; Chan, Emily; Goldberg, Richard M.; Gill, Sharlene; Kahlenberg, Morton S.; Quesenberry, James T.; Thibodeau, Stephen N; Smyrk, Thomas Christopher; Grothey, Axel F; Sinicrope, Frank A; Webb, Thomas A.; Farr, Gist H.; Pockaj, Barbara A; Berenberg, Jeffrey L.; Mooney, Margaret; Sargent, Daniel J.; Alberts, Steven Robert.

In: Clinical Colorectal Cancer, Vol. 13, No. 2, 2014, p. 100-109.

Research output: Contribution to journalArticle

Huang, J, Nair, SG, Mahoney, MR, Nelson, GD, Shields, AF, Chan, E, Goldberg, RM, Gill, S, Kahlenberg, MS, Quesenberry, JT, Thibodeau, SN, Smyrk, TC, Grothey, AF, Sinicrope, FA, Webb, TA, Farr, GH, Pockaj, BA, Berenberg, JL, Mooney, M, Sargent, DJ & Alberts, SR 2014, 'Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147', Clinical Colorectal Cancer, vol. 13, no. 2, pp. 100-109. https://doi.org/10.1016/j.clcc.2013.12.002
Huang, Jocelin ; Nair, Suresh G. ; Mahoney, Michelle R. ; Nelson, Garth D. ; Shields, Anthony F. ; Chan, Emily ; Goldberg, Richard M. ; Gill, Sharlene ; Kahlenberg, Morton S. ; Quesenberry, James T. ; Thibodeau, Stephen N ; Smyrk, Thomas Christopher ; Grothey, Axel F ; Sinicrope, Frank A ; Webb, Thomas A. ; Farr, Gist H. ; Pockaj, Barbara A ; Berenberg, Jeffrey L. ; Mooney, Margaret ; Sargent, Daniel J. ; Alberts, Steven Robert. / Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147. In: Clinical Colorectal Cancer. 2014 ; Vol. 13, No. 2. pp. 100-109.
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title = "Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147",
abstract = "Background Two arms with FOLFIRI, with or without cetuximab, were initially included in the randomized phase III intergroup clinical trial NCCTG (North Central Cancer Treatment Group) N0147. When other contemporary trials demonstrated no benefit to using irinotecan as adjuvant therapy, the FOLFIRI-containing arms were discontinued. We report the clinical outcomes for patients randomized to FOLFIRI with or without cetuximab. Patients and Methods After resection, patients were randomized to 12 biweekly cycles of FOLFIRI, with or without cetuximab. KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation status was retrospectively determined in a central lab. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS) and toxicity. Results One hundred and six patients received FOLFIRI and 40 received FOLFIRI plus cetuximab. Median follow-up was 5.95 years (range, 0.1-7.0 years). The addition of cetuximab showed a trend toward improved DFS (hazard ratio [HR], 0.53; 95{\%} CI, 0.26-1.1; P =.09) and OS (HR, 0.45; 95{\%} CI, 0.17-1.16; P =.10) in the overall group, regardless of KRAS status, and in patients with wild type KRAS. Grade ≥ 3 nonhematologic adverse effects were significantly increased in the cetuximab versus FOLFIRI-alone arm (68{\%} vs. 46{\%}; P =.02). Adjuvant FOLFIRI resulted in a 3-year DFS less than that expected for FOLFOX. Conclusion In this small randomized subset of patients with resected stage III colon cancer, the addition of cetuximab to FOLFIRI was associated with a nonsignificant trend toward improved DFS and OS. Nevertheless, considering the limitations of this analysis, FOLFOX without the addition of a biologic agent remains the standard of care for adjuvant therapy in resected stage III colon cancer.",
keywords = "Adjuvant therapy, Disease free survival, Overall survival, Response rate",
author = "Jocelin Huang and Nair, {Suresh G.} and Mahoney, {Michelle R.} and Nelson, {Garth D.} and Shields, {Anthony F.} and Emily Chan and Goldberg, {Richard M.} and Sharlene Gill and Kahlenberg, {Morton S.} and Quesenberry, {James T.} and Thibodeau, {Stephen N} and Smyrk, {Thomas Christopher} and Grothey, {Axel F} and Sinicrope, {Frank A} and Webb, {Thomas A.} and Farr, {Gist H.} and Pockaj, {Barbara A} and Berenberg, {Jeffrey L.} and Margaret Mooney and Sargent, {Daniel J.} and Alberts, {Steven Robert}",
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doi = "10.1016/j.clcc.2013.12.002",
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pages = "100--109",
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TY - JOUR

T1 - Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147

AU - Huang, Jocelin

AU - Nair, Suresh G.

AU - Mahoney, Michelle R.

AU - Nelson, Garth D.

AU - Shields, Anthony F.

AU - Chan, Emily

AU - Goldberg, Richard M.

AU - Gill, Sharlene

AU - Kahlenberg, Morton S.

AU - Quesenberry, James T.

AU - Thibodeau, Stephen N

AU - Smyrk, Thomas Christopher

AU - Grothey, Axel F

AU - Sinicrope, Frank A

AU - Webb, Thomas A.

AU - Farr, Gist H.

AU - Pockaj, Barbara A

AU - Berenberg, Jeffrey L.

AU - Mooney, Margaret

AU - Sargent, Daniel J.

AU - Alberts, Steven Robert

PY - 2014

Y1 - 2014

N2 - Background Two arms with FOLFIRI, with or without cetuximab, were initially included in the randomized phase III intergroup clinical trial NCCTG (North Central Cancer Treatment Group) N0147. When other contemporary trials demonstrated no benefit to using irinotecan as adjuvant therapy, the FOLFIRI-containing arms were discontinued. We report the clinical outcomes for patients randomized to FOLFIRI with or without cetuximab. Patients and Methods After resection, patients were randomized to 12 biweekly cycles of FOLFIRI, with or without cetuximab. KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation status was retrospectively determined in a central lab. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS) and toxicity. Results One hundred and six patients received FOLFIRI and 40 received FOLFIRI plus cetuximab. Median follow-up was 5.95 years (range, 0.1-7.0 years). The addition of cetuximab showed a trend toward improved DFS (hazard ratio [HR], 0.53; 95% CI, 0.26-1.1; P =.09) and OS (HR, 0.45; 95% CI, 0.17-1.16; P =.10) in the overall group, regardless of KRAS status, and in patients with wild type KRAS. Grade ≥ 3 nonhematologic adverse effects were significantly increased in the cetuximab versus FOLFIRI-alone arm (68% vs. 46%; P =.02). Adjuvant FOLFIRI resulted in a 3-year DFS less than that expected for FOLFOX. Conclusion In this small randomized subset of patients with resected stage III colon cancer, the addition of cetuximab to FOLFIRI was associated with a nonsignificant trend toward improved DFS and OS. Nevertheless, considering the limitations of this analysis, FOLFOX without the addition of a biologic agent remains the standard of care for adjuvant therapy in resected stage III colon cancer.

AB - Background Two arms with FOLFIRI, with or without cetuximab, were initially included in the randomized phase III intergroup clinical trial NCCTG (North Central Cancer Treatment Group) N0147. When other contemporary trials demonstrated no benefit to using irinotecan as adjuvant therapy, the FOLFIRI-containing arms were discontinued. We report the clinical outcomes for patients randomized to FOLFIRI with or without cetuximab. Patients and Methods After resection, patients were randomized to 12 biweekly cycles of FOLFIRI, with or without cetuximab. KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation status was retrospectively determined in a central lab. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS) and toxicity. Results One hundred and six patients received FOLFIRI and 40 received FOLFIRI plus cetuximab. Median follow-up was 5.95 years (range, 0.1-7.0 years). The addition of cetuximab showed a trend toward improved DFS (hazard ratio [HR], 0.53; 95% CI, 0.26-1.1; P =.09) and OS (HR, 0.45; 95% CI, 0.17-1.16; P =.10) in the overall group, regardless of KRAS status, and in patients with wild type KRAS. Grade ≥ 3 nonhematologic adverse effects were significantly increased in the cetuximab versus FOLFIRI-alone arm (68% vs. 46%; P =.02). Adjuvant FOLFIRI resulted in a 3-year DFS less than that expected for FOLFOX. Conclusion In this small randomized subset of patients with resected stage III colon cancer, the addition of cetuximab to FOLFIRI was associated with a nonsignificant trend toward improved DFS and OS. Nevertheless, considering the limitations of this analysis, FOLFOX without the addition of a biologic agent remains the standard of care for adjuvant therapy in resected stage III colon cancer.

KW - Adjuvant therapy

KW - Disease free survival

KW - Overall survival

KW - Response rate

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DO - 10.1016/j.clcc.2013.12.002

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JO - Clinical Colorectal Cancer

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