Association of post-operative CEA with survival and oxaliplatin benefit in patients with stage II colon cancer: a post hoc analysis of the MOSAIC trial

Edouard Auclin, Thierry André, Julien Taieb, Maria Banzi, Jean-Luc Van Laethem, Josep Tabernero, Tamas Hickish, Aimery de Gramont, Dewi Vernerey, Edouard Auclin, Thierry André, Julien Taieb, Maria Banzi, Jean-Luc Van Laethem, Josep Tabernero, Tamas Hickish, Aimery de Gramont, Dewi Vernerey

Abstract

Background: Adjuvant treatment for stage II colon cancer (CC) can be proposed to patients with high-risk disease. Recently, 2.35 ng/mL carcinoembryonic antigen (CEA) was identified as the best cut-off value. This post hoc analysis of the MOSAIC trial assessed post-operative CEA prognostic value for survival outcomes and predictive value for the addition of oxaliplatin to adjuvant treatment.

Methods: Prognostic and predictive values of post-operative CEA in patients with stage II CC were evaluated with Kaplan-Meier survival curves and Cox model with interaction terms. Disease-free survival (DFS) and overall survival (OS) were estimated.

Results: Among 899 stage II CC patients, post-operative CEA was available in 867 (96.4%); and 434 (48.65%) had a high-risk stage II disease. The 3-year DFS rate was 88.5% and 78.7% in the ≤ 2.35 ng/mL and > 2.35 ng/mL group, respectively (P = 0.006). Use of oxaliplatin showed survival benefit only in patients with high-risk stage II CC and post-operative CEA > 2.35 ng/ml (interaction term P = 0.09 and 0.03 for DFS and OS).

Conclusion: CEA is a strong prognostic factor for DFS and OS in stage II CC. In the MOSAIC trial, only high-risk stage II CC patients with post-operative CEA > 2.35 ng/mL benefited from the addition of oxaliplatin to LV5FU2.

Trial registration: NCT00275210 (January 11, 2006).

Conflict of interest statement

Thierry André: Honoraria—AMGEN; Bayer; Bristol-Myers Squibb; PRMA Consulting; Roche/Genentech; Sanofi; SERVIER; Xbiotech. Consulting or Advisory Role—Amgen; Bayer; Bristol-Myers Squibb; Guardant Health; HalioDX; MSD Oncology; Mundipharma; Roche/Genentech; SERVIER. Travel, Accommodations, Expenses—Amgen; Bristol-Myers Squibb; MSD Oncology; Roche/Genentech. Julien Taieb: Consulting or Advisory Role—Amgen; Baxalta; Celgene; Lilly; Merck KGaA; Roche; SERVIER; Sirtex Medical. Speakers’ Bureau—Amgen; Baxalta; Lilly; Merck; Roche/Genentech; Sanofi; SERVIER. Maria Banzi: Honoraria—Merck; Roche (I). Travel, Accommodations, Expenses—Merck; Pfizer; Roche. Josep Tabernero: Consulting or Advisory Role—Amgen; Boehringer Ingelheim; Celgene; Chugai Pharma; ImClone Systems; Lilly; Merck; Merck Serono; Millennium; Novartis; Roche/Genentech; Sanofi; Taiho Pharmaceutical. Tamas Hickish: Stock and Other Ownership Interests—Knowledge To Practice. Patents, Royalties, Other Intellectual Property—Bournemouth University (Inst). Travel, Accommodations, Expenses—Philips Healthcare; XBiotech. Aimery De Gramont: Honoraria—Chugai Pharma; Yakult. Dewi Vernerey: Consulting or Advisory Role—HalioDx; Janssen-Cilag; OSE Immunotherapeutics; Prestizia. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Association between CEA and DFS (a) or OS (b) by the restricted cubic splines method
Fig. 2
Fig. 2
DFS according to (a) CEA 5 ng/mL and CEA 2.35 ng/mL (b)
Fig. 3
Fig. 3
Benefit for DFS with the addition of oxaliplatin to LV5FU2 in a all patients, b the MOSAIC low-risk patients, c the MOSAIC low-risk patients after CEA stratification, d the MOSAIC high-risk patients, and e the MOSAIC high-risk patients after CEA stratification. Figure 3 abbreviations: Ox oxaliplatin; +ox with oxaliplatin; Ox without oxaliplatin
Fig. 4
Fig. 4
Benefit for OS with the addition of oxaliplatin to LV5FU2 in (a) all patients, (b) the MOSAIC low-risk patients, (c) the MOSAIC low-risk patients after CEA stratification, (d) the MOSAIC high-risk patients, and (e) the MOSAIC high-risk patients after CEA stratification. Figure 4 abbreviations: Ox: oxaliplatin; + ox: with oxaliplatin; Ox: without oxaliplatin

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