Role of Deficient DNA Mismatch Repair Status in Patients With Stage III Colon Cancer Treated With FOLFOX Adjuvant Chemotherapy: A Pooled Analysis From 2 Randomized Clinical Trials
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Contributors
Abstract
IMPORTANCE: The prognostic impact of DNA mismatch repair (MMR) status in stage III colon cancer patients receiving FOLFOX (folinic acid, fluorouracil, and oxaliplatin) adjuvant chemotherapy remains controversial.
OBJECTIVE: To determine the association of MMR status with disease-free survival (DFS) in patients with stage III colon cancer treated with FOLFOX.
DESIGN, SETTING, AND PARTICIPANTS: The evaluated biomarkers for MMR status were determined from prospectively collected tumor blocks from patients treated with FOLFOX in 2 open-label, phase 3 randomized clinical trials: NCCTG N0147 and PETACC8. The studies were conducted in general community practices, private practices, and institutional practices in the United States and Europe. All participants had stage III colon adenocarcinoma. They were enrolled in NCCTG N0147 from February 2004 to November 2009 and in PETACC8 from December 2005 to November 2009.
INTERVENTIONS: Patients in the clinical trials were randomly assigned to receive 6 months of chemotherapy with FOLFOX or FOLFOX plus cetuximab. Only those patients treated with FOLFOX alone were included in the present study.
MAIN OUTCOMES AND MEASURES: Association of MMR status with DFS was analyzed using a stratified Cox proportional hazards model. Multivariable models were adjusted for age, sex, tumor grade, pT/pN stage, tumor location, ECOG (Eastern Cooperative Oncology Group) performance status, and BRAF V600E mutational status.
RESULTS: Among 2636 patients with stage III colon cancer treated with FOLFOX, MMR status was available for 2501. Of these, 252 (10.1%) showed deficient MMR status (dMMR; 134 women, 118 men; median age, 59 years), while 2249 (89.9%) showed proficient MMR status (pMMR; 1020 women, 1229 men; median age, 59 years). The 3-year DFS rates in the dMMR and pMMR groups were 75.6% and 74.4%, respectively. By multivariate analysis, patients with dMMR phenotype had significantly longer DFS than those with pMMR (adjusted hazard ratio, 0.73; 95% CI, 0.54-0.97; P = .03).
CONCLUSIONS AND RELEVANCE: The deficient MMR phenotype remains a favorable prognostic factor in patients with stage III colon cancer receiving FOLFOX adjuvant chemotherapy.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00079274 for the NCCTG N0147 trial and EudraCT identifier: 2005-003463-23 for the PETACC8 trial.
Details
Original language | English |
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Pages (from-to) | 379-383 |
Number of pages | 5 |
Journal | JAMA oncology |
Volume | 4 |
Issue number | 3 |
Publication status | Published - 1 Mar 2018 |
Peer-reviewed | Yes |
External IDs
PubMedCentral | PMC5784452 |
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Scopus | 85047476912 |
ORCID | /0000-0002-9321-9911/work/142251974 |
Keywords
Sustainable Development Goals
Keywords
- Adenocarcinoma/drug therapy, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Brain Neoplasms/epidemiology, Cetuximab/administration & dosage, Chemotherapy, Adjuvant, Clinical Trials, Phase III as Topic/methods, Colonic Neoplasms/drug therapy, Colorectal Neoplasms/epidemiology, DNA Mismatch Repair/genetics, DNA Mutational Analysis, Female, Fluorouracil/therapeutic use, Humans, Leucovorin/therapeutic use, Male, Middle Aged, Mutation, Neoplasm Staging, Neoplastic Syndromes, Hereditary/epidemiology, Organoplatinum Compounds/therapeutic use, Randomized Controlled Trials as Topic/methods, Treatment Outcome