Defective Mismatch Repair status as a prognostic biomarker of disease-free survival in stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy
Menée sur 303 patients atteints d'un cancer du côlon de stade III et traités à l'aide du protocole de chimiothérapie FOLOFOX dans neuf centres hospitaliers français, cette étude évalue l'association entre le statut tumoral de la réparation des défauts d'appariement de l'ADN et la réponse thérapeutique
Purpose: Adding oxaliplatin to adjuvant 5-fluorouracil (5FU) chemotherapy improves 3-year disease-free survival (DFS) after resection of stage III colon cancer. Several studies suggest that patients with tumors exhibiting defective mismatch repair (MMR) do not benefit from adjuvant 5FU chemotherapy, but there are few data on 5FU-oxaliplatin (FOLFOX) adjuvant chemotherapy in this setting. The aim of this study was to evaluate the prognostic value of MMR status for DFS in patients with stage III colon cancer receiving adjuvant FOLFOX chemotherapy. Experimental Design: MMR status was determined by MSI testing or immunohistochemistry in 303 unselected patients with stage III colon cancer receiving adjuvant FOLFOX chemotherapy in nine centers. Cox proportional hazards models were used to examine the association between MMR status and 3-year DFS. Results: The 3-year DFS rate was significantly higher in the 34 patients (11.2% of the study population) with defective MMR tumors (90.5%) than in patients with proficient MMR tumors (73.8%) (log rank test; HR, 2.16; 95% CI, 1.09-4.27; P = 0.027). In multivariate analysis, MMR status remained an independent significant prognostic factor for DFS (HR, 4.48; 95% CI, 1.34-14.99; P = 0.015). Conclusion: MMR status is an independent prognostic biomarker for DFS in stage III colon cancer patients receiving adjuvant FOLFOX chemotherapy.
Clinical Cancer Research , résumé, 2011