Meeting
2014 ASCO Annual Meeting
AIO KRK0306, FIRE3 trial: CEA and CA19-9 influence outcome of patients with KRAS exon wild-type metastatic colorectal cancer (mCRC) receiving first-line therapy with FOLFIRI plus cetuximab or bevacizumab.
Authors
Marlies Michl
Department of Hematology and Oncology, Klinikum Großhadern and Comprehensive Cancer Center, LMU Munich, Munich, Germany
Marlies Michl , Ludwig Fischer von Weikersthal , Alexander Crispin , Thomas Decker , Alexander Kiani , Ursula Vehling-Kaiser , Salah-Eddin Al-Batran , Tobias Heintges , Christian A. Lerchenmuller , Christoph Kahl , Gernot Seipelt , Frank Kullmann , Martina Stauch , Werner Scheithauer , Joerg Hielscher , Michael Scholz , Sebastian Mueller , Dominik Paul Modest , Sebastian Stintzing , Volker Heinemann
Organizations
Department of Hematology and Oncology, Klinikum Großhadern and Comprehensive Cancer Center, LMU Munich, Munich, Germany, Health Center St. Marien GmbH, Amberg, Germany, Department of Medical Information Progressing, Biometry and Bioinformatics, University Hospital Grosshadern, LMU Munich, Munich, Germany, Onkonet - Onkologie Ravensburg, Ravensburg, Germany, Klinikum Bayreuth, Bayreuth, Germany, Practice for Medical Oncology, Landshut, Germany, Krankenhaus Nordwest, Frankfurt, Germany, Städtisches Klinikum Neuss Lukaskrankenhaus GmbH, Medical Department II, Neuss, Germany, Private Practice for Oncology, Muenster, Germany, Department for Hematology, Klinikum Magdeburg, Magdeburg, Germany, Onkologische Schwerpunktpraxis, Bad Soden, Germany, 1st Department of Medicine, Nordoberpfalz Hospital Weiden, Weiden, Germany, Onkologische Schwerpunktpraxis Kronach, Kronach, Germany, Medical University of Vienna, Vienna, Austria, Klinikum Chemnitz gGmbH, Klinik fuer Allgemein- und Viszeralchirurgie, Chemnitz, Germany, Klinikum Stuttgart, Innere Medizin, Stuttgart, Germany, Ambulantes Onkologie Centrum, Ansbach, Germany, Department of Hematology and Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, LMU Munich, Munich, Germany
Research Funding
Pharmaceutical/Biotech Company
Background: To examine the impact of tumor marker response of carcinoembryonic antigen (CEA) and carbohydrate-antigen 19-9 (CA19-9) on overall survival (OS) and progression free survival (PFS) in patients with KRAS wild-type mCRC receiving first line chemotherapy in the FIRE3-trial comparing FOLFIRI + cetuximab (cet) vs. FOLFIRI + bevacizumab (bev). Methods: Baseline tumor marker levels, the time to nadir (in days; d) and the percentage of tumor marker decrease observed at the nadir compared with baseline were analyzed. The percentage was 0 for no change and negative if the tumor marker increased. Comparisons relied on Mann-Whitney U tests for independent groups and Wilcoxon signed-rank tests for dependent ones. ROC analysis resulted in a cut-off value using the maximum of sensitivity and specificity for best response. Results: For analysis of CEA, 472/592 pts (cet arm: 230 pts; bev arm: 242 pts) were eligible and for CA19-9, 439/592 pts (cet arm: 209 pts; bev arm: 230 pts). Baseline CEA (log) and CA19-9 (log) levels both significantly correlated with OS (p=0.008 and p<0.0001, respectively), but not with PFS (p=0.26 and p=0.15, respectively). For CEA and CA19-9 median time to nadir was comparable for both study arms, however in all patients CA19-9 nadir occurred earlier than CEA nadir (p<0.0001). Extent of CEA nadir significantly differed between treatment arms (cet arm: median: 83.0%; IQR: 40.9%-94.7%; bev arm: median: 72.3%; IQR: 26.3%-91.0%; p=0.003). A similiar trend was observed for CA19-9 nadir (cet arm: median: 64.3%; IQR: 13.4%-90.7%; bev arm: 47.0%; IQR: 1.7%-86.4%; p=0.085). In univariate analysis, a CEA decrease of more than 75% correlated with longer OS (33.2 vs. 22.9 mo; p<0.0001; HR 0.63; 95%Cl: 0.50–0.80) and PFS (11.7 vs. 9.0 mo; p=0.007; HR 0.67; 95%Cl: 0.62–0.93). Conclusions: In this analysis, we demonstrate that a greater decrease of CEA during therapy correlates with longer survival and the depth of CEA decrease is significantly greater in the cetuximab-arm compared to the bevacizumab-arm. Clinical trial information: NCT00433927.
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Abstract Details
Session Type
Poster Session
Session Title
Gastrointestinal (Colorectal) Cancer
Track
Gastrointestinal Cancer—Colorectal and Anal
Sub Track
Colorectal Cancer
Clinical Trial Registration Number
NCT00433927
Citation
J Clin Oncol 32:5s, 2014 (suppl; abstr 3592^)
DOI
10.1200/jco.2014.32.15_suppl.3592
Abstract #
3592^
Poster Bd #
55
Abstract Disclosures
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