DNA Mismatch Repair Status in Patients With Advanced Colon Cancer

Submitted by admin5 on Wed, 10/11/2017 - 13:16

A pooled analysis investigated the prognostic role of DNA mismatch repair (MMR) status in patients with stage III colon cancer treated with a standard adjuvant chemotherapy regimen, published in JAMA Oncology (online October 5, 2017; doi:10.1001/jamaoncol.2017.2899).

The combination regimen of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) remains the consensus standard of care for treating late-stage colon adenocarcinoma after surgery. However, the prognostic impact of DNA MMR status in patients receiving adjuvant FOLFOX for stage III disease remains controversial.

Aziz Zaanan, MD, PhD, departments of medicine and oncology, Mayo Clinic (Rochester, MN), and colleagues conducted a pooled analysis to determine the association of DNA MMR status with disease-free survival in patients with stage III colon adenocarcinoma treated with adjuvant FOLFOX. Researchers evaluated biomarkers for DNA MMR status of prospectively collected tumor blocks from patients in multiple open-label, phase III randomized clinical trials: NCCTG N0147 and PETACC8. In both trials, patients were received either 6 months of FOLFOX alone or FOLFOX plus cetuximab. Only patients treated with FOLFOX alone and with available DNA MMR status (n = 2501) were included in the pooled analysis.

A stratified Cox proportional hazards model was used to analyze the association of DNA MMR status with disease-free survival.

Researchers reported that 10.1% of patients (n = 252) exhibited deficient MMR status, while the remaining 89.9% (n = 2249) showed proficient MMR status. Three-year disease-free survival rates in the deficient MMR and proficient MMR groups were 75.6% and 74.4%, respectively.

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Additionally, a multivariable analysis—which adjusted for age, sex, tumor grade, pT/pN stage, tumor location, Eastern Cooperative Oncology Group performance status, and BRAF V600E mutation status—showed that patients with deficient MMR phenotype benefited from significantly longer disease-free survival than those with proficient MMR status (HR, 0.73; 95% CI, 0.54-0.97; P = .03).

Researchers concluded that deficient MMR phenotype should be considered a favorable prognostic indicator in patients with stage III colon adenocarcinoma receiving adjuvant FOLFOX. “Future clinical trials in the adjuvant setting should consider this molecular characteristic as an important stratification factor,” they wrote.—Zachary Bessette