Meeting
2019 ASCO Annual Meeting
Is the predictive and prognostic impact of sporadic and familial microsatellite instable stage III colon cancer different? A pooled analysis of the PETACC8 and NCCTG N0147 (Alliance) trials.
Authors
Aziz Zaanan
Hopital Européen Georges Pompidou, Paris, France
Aziz Zaanan , Qian Shi , Julien Taieb , Steven R Alberts , Jeffrey P. Meyers , Thomas C. Smyrk , Catherine Julié , Ayman Zawadi , Josep Tabernero , Enrico Mini , Richard M. Goldberg , Gunnar Folprecht , Jean Luc VAN Laethem Sr., Karine Le Malicot , Daniel J. Sargent , Pierre Laurent-Puig , Frank A. Sinicrope
Organizations
Hopital Européen Georges Pompidou, Paris, France, Department of Health Science Research, Mayo Clinic, Rochester, MN, Hôpital Européen Georges-Pompidou, Sorbonne Paris Cite/Paris Descartes University, Paris, France, Mayo Clinic, Rochester, MN, Mayo Clinic Cancer Center, Rochester, MN, Ambroise Paré Hospital and Versailles Saint-Quentin-en-Yvelines University, Boulogne-Billancourt, France, Radiothérapie, Centre Hospitalier Départemental, La Roche Sur Yon, France, Vall d’Hebron University Hospital and Institute of Oncology, Barcelona, Spain, Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy, West Virginia University Cancer Institute, Morgantown, WV, University Hospital Carl Gustav Carus, Dresden, Germany, Hôpital Universitaire Erasme, Bruxelles, Belgium, FFCD and INSERM U1231, Dijon, France, Paris Descartes University, Paris, France
Research Funding
Pharmaceutical/Biotech Company
U.S. National Institutes of Health, UNIH Award Numbers : 10CA180821, U10CA180882, U24CA196171
Background: The Microsatellite instability (MSI) or deficient mismatch repair (dMMR) phenotype is usually taken as a single biological entity whereas no data are available concerning prognosis and response to chemotherapy between sporadic and familial dMMR cases. Methods: Resected KRAS exon 2 wild-type (WT) tumor stage III colon cancers (N = 4596) from patients (pts) randomly assigned to FOLFOX +/- cetuximab in two adjuvant large phase III trials were prospectively analyzed for MSI status and dMMR mechanism (sporadic vs familial). Stratified Cox models were used to assess prognostic and predictive values of dMMR mechanism by treatment arms, adjusting for age, gender, tumor grade, ECOG PS, pT/pN stage and primary tumor location. Results: Among dMMR patients with complete data for dMMR mechanism analysis (N = 354), there were 255 (72%) sporadic (BRAF mutated or WT with MLH1 methylation) and 99 (28%) familial (loss of MSH2 or MSH6, or loss MLH1 with BRAF WT and unmethylated MLH1) cases. A large proportion of dMMR sporadic cases were mutated for BRAF (n = 200; 80%). In pts treated with FOLFOX, the disease-free survival (DFS) was not statistically different by dMMR mechanism, while for pts treated with FOLFOX + cetuximab, the sporadic cases did worse than familial cases (DFS; adjusted (adj) HR, 2.69; 95% CI, 1.02-7.08; P= 0.04). Considering the predictive value, a deleterious effect of adding cetuximab to FOLFOX was observed in sporadic (DFS; adjHR, 1.68; 95% CI, 1.01-2.79; P= 0.04) but not in familial dMMR pts (interaction P value regarding treatment effect = 0.03). Furthermore, a non-significant trend to a deleterious effect of adding cetuximab to FOLFOX was observed in BRAF mutant (DFS; adjHR, 1.66; 95% CI, 0.95-2.92; P= 0.07) but not in BRAF WT pts. Conclusions: The addition of cetuximab to FOLFOX was associated with reduced DFS in patients with sporadic dMMR cases. Further studies including the methylator phenotype (CIMP) analysis are needed to validate these results. Clinical trial information: NCT00265811 and NCT00079274
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Abstract Details
Session Type
Poster Session
Session Title
Gastrointestinal (Colorectal) Cancer
Track
Gastrointestinal Cancer—Colorectal and Anal
Sub Track
Epidemiology/Outcomes
Clinical Trial Registration Number
NCT00265811 and NCT00079274
Citation
J Clin Oncol 37, 2019 (suppl; abstr 3583)
DOI
10.1200/JCO.2019.37.15_suppl.3583
Abstract #
3583
Poster Bd #
75
Abstract Disclosures
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