Biweekly Cetuximab Plus FOLFOX6 as First-Line Therapy in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The CEBIFOX Trial.

Abstract

BACKGROUND:

The multicenter, single-arm, phase II study CEBIFOX evaluated the efficacy of a biweekly cetuximab administration in combination with FOLFOX6 as first-line therapy in KRAS (exon 2) wild-type (wt) metastatic colorectal cancer (mCRC).

PATIENTS AND METHODS:

Patients received FOLFOX6 with cetuximab (500 mg/m2) every second week. Primary endpoint was objective response rate (ORR), among others secondary endpoints were safety, progression-free survival (PFS), overall survival (OS), and patient-reported outcome (PRO). The impact on the treatment efficacy was evaluated in explorative subgroup analyses, including extended molecular profiling and primary tumor location.

RESULTS:

In total, 57 were included in the intention-to-treat (ITT) analyses. New RAS mutations were detected in 14.0% by post hoc next-generation sequencing analysis in 43 patients. The ORR in the all RASwt population was 70.3% with a median PFS and OS of 10.9 (95% confidence interval [CI], 9.0-12.9) and 33.8 (95% CI, 21.1-45.5) months. Grade 3-5 adverse events occurred in 66.7% of the ITT, without significant impact on the PRO. Patients with right-sided primary tumors had a reduced ORR (54.5%), and median PFS and OS (10.1 and 23.8 months). BRAF mutations were detected in 11.3%. These patients had a significantly lower ORR, and median PFS and OS. Patients with RASwt/BRAFwt tumors had a notably high median PFS and OS of 14.3 and 38.9 months.

CONCLUSIONS:

This study supports the efficacy and safety of biweekly cetuximab given in combination with FOLFOX6 in patients with RASwt/BRAFwt mCRC with left-sided primary tumor. CEBIFOX is the first trial reporting the complete dataset, including extended molecular profiling and tumor location of a biweekly administered cetuximab/FOLFOX6 in mCRC. Clinical trial number: NCT01051167.

• Authors: Stefan Kasper, Johannes Meiler, Heike Knipp, Thomas Höhler, Peter Reimer, Tilman Steinmetz, Winfried Berger, Gabriele Linden, Henning Reis, Peter Markus, Andreas Paul, Alexander Dechêne, Brigitte Schumacher, Karina Kostbade, Isabel Virchow, Saskia Ting, Karl Worm, Kurt W Schmid, Thomas Herold, Marcel Wiesweg, Martin Schuler, Tanja Trarbach
• Journal: Clinical colorectal cancer (Clin Colorectal Cancer) Vol. 19 Issue 4 Pg. 236-247.e6 (12 2020) ISSN: 1938-0674 [Electronic] United States
• PMID: 32737003 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• KRAS protein, human
• Organoplatinum Compounds
• Proto-Oncogene Proteins p21(ras)
• Cetuximab
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Cetuximab (administration & dosage, adverse effects)
• Colorectal Neoplasms (drug therapy, genetics, mortality, pathology)
• Drug Administration Schedule
• Exons (genetics)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Leucovorin (administration & dosage, adverse effects)
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Progression-Free Survival
• Proto-Oncogene Proteins p21(ras) (genetics)
• Young Adult