TY - JOUR
T1 - 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
AU - Zaanan, Aziz
AU - Shi, Qian
AU - Taieb, Julien
AU - Alberts, Steven R.
AU - Meyers, Jeffrey P.
AU - Smyrk, Thomas C.
AU - Julie, Catherine
AU - Zawadi, Ayman
AU - Tabernero, Josep
AU - Mini, Enrico
AU - Goldberg, Richard M.
AU - Folprecht, Gunnar
AU - Van Laethem, Jean Luc
AU - Le Malicot, Karine
AU - Sargent, Daniel J.
AU - Laurent-Puig, Pierre
AU - Sinicrope, Frank A.
N1 - Funding Information:
Funding/Support: Dr Zaanan is supported by the
Funding Information:
“French National Society of Gastroenterology” (SNFGE: Société Nationale Française de Gastro-Entérologie) (Bourse Robert Tournut). The PETACC8 study was sponsored by the Fédération Francophone de Cancérologie Digestive (FFCD) that was responsible for the study management. Merck KGaA and Sanofi-Aventis supported the PETACC8 study: Merck provided the study cetuximab and financial support for study management; Sanofi-Aventis provided financial support for the provision of oxaliplatin to Belgian sites when necessary. The N0147 trial was conducted as a collaborative trial of the North Central Cancer Treatment Group (NCCTG), Mayo Clinic, which is now part of the Alliance for Clinical Trials in Oncology. The study was supported in part by grants from the US National Cancer Institute of the National Institutes of Health under Award Numbers U10CA025224, the NCCTG Biospecimen Resource (U24CA114740), and the Alliance for Clinical Trials in Oncology (U10CA031946, U10CA033601, U10CA1808821 and U10CA180882). Bristol-Myers Squibb provided cetuximab to the NCCTG for conduct of the study. The present study was also supported in part by funds from Bristol-Myers Squibb, ImClone Systems Inc, Sanofi Aventis, and Pfizer.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
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U2 - 10.1001/jamaoncol.2017.2899
DO - 10.1001/jamaoncol.2017.2899
M3 - Article
C2 - 28983557
AN - SCOPUS:85047476912
VL - 4
SP - 379
EP - 383
JO - JAMA oncology
JF - JAMA oncology
SN - 2374-2437
IS - 3
ER -