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.

• Authors: 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 C Smyrk, Axel Grothey, Frank A Sinicrope, Thomas A Webb, Gist H Farr Jr, Barbara A Pockaj, Jeffrey L Berenberg, Margaret Mooney, Daniel J Sargent, Steven R Alberts, Alliance for Clinical Trials in Oncology
• Journal: Clinical colorectal cancer (Clin Colorectal Cancer) Vol. 13 Issue 2 Pg. 100-9 (Jun 2014) ISSN: 1938-0674 [Electronic] United States
• PMID: 24512953 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• KRAS protein, human
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins p21(ras)
• ras Proteins
• Cetuximab
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Camptothecin (adverse effects, analogs & derivatives, therapeutic use)
• Cetuximab
• Chemotherapy, Adjuvant
• Colonic Neoplasms (drug therapy, pathology, surgery)
• Disease-Free Survival
• Female
• Fluorouracil (adverse effects, therapeutic use)
• Follow-Up Studies
• Humans
• Leucovorin (adverse effects, therapeutic use)
• Male
• Middle Aged
• Mutation
• Neoplasm Staging
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins p21(ras)
• Survival Rate
• Treatment Outcome
• ras Proteins (genetics)