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Deficient Mismatch Repair Extends Disease-Free Survival in CRC

Jaime Rosenberg
Patients with stage III colon cancer with deficient DNA mismatch repair (MMR) genes who are treated with FOLFOX have a more favorable prognosis than those with proficient MMRs.
Results from a recent study show that deficient DNA mismatch repair (MMR) was highly associated with longer disease-free survival (DFS) in patients with stage III colon cancer being treated with FOLFOX.

The study, published by JAMA Oncology, analyzed data from 2 randomized clinical trials: NCCTG N0147 and PETACC8. Patients were enrolled in the NCTG N1047 trial from February 2004 to November 2009 and In PETACC8 from December 2005 to November 2009.

MMR status was accessible for 2501 patients being treated with FOLFOX, 252 of whom showed deficient MMR status and 2249 showed proficient MMR status. The 3-year DFS in the deficient MMR status was 75.6% and in the proficient MMR status was 74.4%.

MMR status was determined by either immunohistochemical (IHC) analysis, or by microsatellite instability (MSI) testing, if IHC testing did not work. Deficient MMRs were characterized as having loss of expression of 1 or more MMR proteins by IHC or exhibiting high-level tumor DNA MSI on MSI testing. Proficient MMRs were characterized as having intact MMR protein expression on IHC or microsatellite-stable or low-level MSI status on MSI testing.

“While most studies have found that patients with dMMR tumors have a more favorable stage-adjusted prognosis, other studies have not detected a significant difference in clinical outcome or have suggested that any favorable prognostic effect of dMMR is limited to patients with earlier-stage tumors,” wrote the authors.

From this study, authors were able to conclude that deficient MMR was significantly associated with longer DFS in patients with stage III colon cancer being treated with FOLFOX alone.

Consistent with other studies was the association of deficient MMRs versus proficient MMRs with older age, female sex, higher T stage, higher tumor grade, and proximal location.

The first data concerning the effect of MMR status came from past studies that suggested the addition of oxaliplatin to fluorouracil may heighten survival rates for patients who had state IIIdeficient MMR colon cancer. Following those studies, post hoc analyses of patients with stage II and III colon cancer from 2 trials indicated that adding oxaliplatin to fluorouracil was autonomous of MMR status. Consistent with these findings, the MOSAIC trial indicated that patients with both categories of MMRs received survival benefits from FOLFOX compared with fluorouacil alone.

Focusing on a single tumor stage (III), along with including prospective tissue biospecimen collection and treatment of patients enrolled in recent large randomized studies, strengthened this study against others.

 
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