Adjuvant chemotherapy (LV5FU2 +/- oxaliplatin) is recommended for high risk (T4 and/or bowel perforation and/or number of nodes examined <10) stage II CC. After curative treatment (ttt), CEA measurement is recommended for follow up. CEA above 5 ng/mL is of poor prognosis, however recently a cut-off of 2.35 was shown to be more appropriate, in a cohort of 40,000 patients (pts). We explored the postoperative CEA prognostic value and its predictive value for the benefit of oxaliplatin addition to LV5FU2 adjuvant chemotherapy.
Stage II CC pts in MOSAIC study with postoperative CEA available were included. Overall (OS) and Disease Free Survival (DFS) were estimated with the Kaplan Meier method. CEA predictive value for benefit of oxaliplatin addition to LV5FU2 on survival was evaluated with an interaction term between treatment and CEA risk group in the Cox model, firstly in the whole stage II population, then according to high/low risk groups.
CEA was available in 867 pts (96.4%), with n = 664 ≤ 2.35 (group 1) and n = 203 > 2.35 (group 2). 3y OS rates were 96%, and 90% in groups 1 and 2, p = 0.02. 3y DFS rates were 88%, and 79%, p = 0.006. There was an interaction between CEA level and ttt arm (LV5FU2 or FOLFOX) for OS (interaction term p = 0.03) and DFS (p = 0.11), Table. This was confirmed in high risk (interaction term p = 0.03 and 0.09, for OS and DFS) but not in low risk stage II CC (p = 1 and 0.78 for OS and DFS), Table. CEA was associated with an improvement of oxaliplatin benefit in OS and DFS in high risk stage II CC pts.Table: 462PD
3y OS and DFS in the MOSAIC stage II pts according to postoperative CEA level and ttt arm
|3y OS %||3y DFS %|
|Whole population||CEA ≤2.35 ng/mL||97.3||93.9||88.2||88.7|
|Low risk||CEA ≤2.35ng/mL||98.8||95.7||91.8||91.5|
|High risk||CEA ≤2.35 ng/mL||95.5||92.5||84.0||86.3|
We validated that postoperative CEA with a CEA cut-off of 2.35 ng/mL was prognostic for OS and DFS in stage II CC. CEA was also predictive of oxaliplatin benefit in OS and DFS for high risk stage II CC. External validation on the CEA predictive value is ongoing and will be presented with this cohort.
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T. Andre: Honoraria: Roche/Genentech, Bristol-Myers Squibb, Servier, xBiotech, Bayer Sanofi, Amgen, PRMA Consulting; Advisory role: Roche/Genentech, Amgen, Bristol-Myers Squibb, Mundipharma International, HalioDX, MSD Oncology, Servier, Guardant Health, Bayer. J. Taieb: Advisory role: Roche, Merck KGaA, Amgen, Lilly, Baxalta, Servier and Sirtex Medical. J. Tabernero: Advisory role: Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Roche, Sanofi, Taiho Pharmaceutical, Genentech/Roche, Merrimack, Symphonu Evolution, Peptomyc. T. Hickish: Research funding: xBiotech, Roche, Pfizer, Novartis, Merck. A. de Gramont: A. Honoraria: Yakult, Chugai Pharma. D. Vernerey: Advisory role: OSE Immunotherapeutics, Janssen-Cilag, Prestizia, HalioDX. All other authors have declared no conflicts of interest.