Effect of adding oxaliplatin to adjuvant 5-fluorouracil/leucovorin (5FU/LV) in patients with defective mismatch repair (dMMR) colon cancer stage II and III included in the MOSIAC study.

Authors

null

Jean-François Flejou

Department of Pathology, Hospital Saint-Antoine, AP-HP, Paris, France

Jean-François Flejou , Thierry André , Benoist Chibaudel , Aurelie Scriva , Tamas Hickish , Josep Tabernero , Jean-Luc Van Laethem , Maria Banzi , Eduard Maartense , Adi Shani , Göran Carlsson , Werner Scheithauer , Demetris Papamichael , Markus Moehler , Stefania Landolfi , Pieter Demetter , Alex Duval , Mark Lee , Soudhir Colote , Aimery De Gramont

Organizations

Department of Pathology, Hospital Saint-Antoine, AP-HP, Paris, France, Hôpital Saint Antoine, Paris, France, Hôpital Saint-Antoine, Paris, France, Royal Bournemouth Hospital, Bournemouth, United Kingdom, Vall d'Hebron University Hospital, Barcelona, Spain, Hôpital Universitaire Erasme, Brussels, Belgium, Arcispedale Santa Maria Nuova, Reggio, Italy, Department of Internal Medicine, Reinier De Graaf Groep, Delft, Netherlands, Sheba Medical Center, Tel HaShomer, Israel, Sahlgrenska University Hospital, Östra, Sweden, Medical University of Vienna, Vienna, Austria, B.O. Cyprus Oncology Centre, Nicosia, Cyprus, Department of Gastroenterology & Hepatology, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany, Hospital Vall d'Hebron, Barcelona, Spain, Erasme University Hospital, Brussels, Belgium, INSERM UMRS 938, Paris, France, Genomic Health, Inc., Redwood City, CA, GERCOR, PARIS, France, Hospital Saint Antoine, Paris, France

Research Funding

Pharmaceutical/Biotech Company

Background: The MOSAIC study (André T, N Engl J Med, 2004) demonstrated that adding oxaliplatin to adjuvant 5FU and LV improved three-year disease-free survival (DFS) in stage II and III resected CC. Efficacy of FOLFOX4 in pts with dMMR stage III was suggested in a retrospective study (Zaanan A, Ann Oncol 2010). Methods: Of the 2,246 pts included in MOSAIC study, formalin-fixed, paraffin-embedded (FFPE) tissue blocks or slides from 1,019 pts were obtained. Thirty-three samples with insufficient tumor tissue were excluded from this translational study. MMR status was determined by immunohistochemistry (IHC) analysis of the protein products of MLH1, MSH2, PMS2, and MSH6 genes. Results: A total of 986 pts (44%) were evaluable for MMR status and MMR status was not evaluable for 1,260 pts (56%). Relapse-free survival (RFS), DFS and overall survival (OS) were similar in both, MMR and MMR not evaluable population. Ninety (9.1%) and 896 (90.9%) pts had dMMR and proficient MMR (pMMR) CC, respectively. Of the patients with 90 dMMR CC, 45 pts had stage II and 45 stage III. Hazard Ratios (HRs) for stage II and III dMMR are 0.52 (0.21–1.28) for RFS, 0.52 (0.24–1.14) for DFS, and 0.45 (0.19–1.05) for OS, respectively. HR for stage III dMMR are 0.56 (0.19–1.61) for RFS, 0.51 (0.18–1.41) for DFS, and 0.44 (0.15–1.34) for OS, respectively. HR for stage II dMMR are 0.64 (0.11–3.70) for RFS, 0.60 (0.17–2.09) for DFS, and 0.52 (0.13–2.10) for OS, respectively. Conclusions: Analyses ofcolon cancerMMR status in pts included in the MOSAIC study support the use of FOLFOX4 in pts with dMMR stage III cancer. Clinical trial information: NCT00275210.

Three-year RFS and DFS and 5- and 10-year OS for patients with dMMR CC.
3-year RFS 3-year DFS 5-year OS 10-year OS
Stage II and III dMMR (n=90)
FOLFOX4 (n=40) 90.0% ± 4.7% 87.5% ± 5.2% 90.0% ± 4.7% 87.2% ± 5.4%
LV5FU2 (n=50) 79.8% ± 5.7% 78.0% ± 5.9% 82.0% ± 5.5% 70.9% ± 6.6%
Stage III dMMR(n=45)
FOLFOX4 (n=17) 82.4% ± 9.2% 82.4% ± 9.2% 88.2% ± 7.8% 88.2% ± 7.8%
LV5FU2 (n=28) 67.9% ± 8.8% 67.9% ± 8.8% 71.3% ± 8.6% 63.0% ± 9.4%
Stage II dMMR (n=45)
FOLFOX4 (n=23) 95.7% ± 4.2% 91.3% ± 5.8% 91.3% ± 5.8% 87.0% ± 7%
LV5FU2 (n=22) 95.2% ± 4.6% 90.9% ± 6.3% 95.5% ± 4.4% 81% ± 8.6%

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Abstract Details

Meeting

2013 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Gastrointestinal (Colorectal) Cancer

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Colorectal Cancer

Clinical Trial Registration Number

NCT00275210

Citation

J Clin Oncol 31, 2013 (suppl; abstr 3524)

DOI

10.1200/jco.2013.31.15_suppl.3524

Abstract #

3524

Poster Bd #

16

Abstract Disclosures