Romain Cohen1,2, Julien Taieb3, Jack Fiskum2, Greg Yothers4, Richard Goldberg5, Takayuki Yoshino6, Steven Alberts7, Carmen Allegra8, Aimery de Gramont9, Jean-Francois Seitz10, Michael O'Connell7, Daniel Haller11, Norman Wolmark12, Charles Erlichman7, Alberto Zaniboni13, Sara Lonardi14, Rachel Kerr15, Axel Grothey16, Frank A Sinicrope7, Thierry André1, Qian Shi2. 1. Sorbonne Université, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, Paris, France. 2. Department of Health Science Research, Mayo Clinic, Rochester, MN. 3. Sorbonne Paris Cité, Paris Descartes University Georges Pompidou European Hospital, Paris, France. 4. Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA. 5. WVU Cancer Institute, West Virginia University, Morgantown, WV. 6. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 7. Department of Oncology, Mayo Clinic, Rochester, MN. 8. Department of Medicine and University of Florida Shands Cancer Center, FL. 9. Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France. 10. Hôpital La Timone, Marseille, France. 11. Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA. 12. University of Pittsburgh, Pittsburgh, PA. 13. Medical Oncology Unit, Fondazione Poliambulanza, Brescia, Italy. 14. Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy. 15. University of Oxford, Oxford, United Kingdom. 16. West Cancer Center, Germantown, TN.
Abstract
PURPOSE: In patients with stage III colon cancer (CC) whose tumors demonstrate microsatellite instability (MSI), the efficacy of adjuvant fluoropyrimidine (FP) with or without oxaliplatin has not been clearly demonstrated and the prognostic value of MSI remains uncertain. MATERIALS AND METHODS: Individual patient data from the ACCENT database were used to evaluate the effect of FP with or without oxaliplatin on disease-free survival (DFS) and overall survival (OS) among patients with MSI stage III CC and the prognostic value of MSI in patients treated with FP plus oxaliplatin, by stratified Cox models adjusted for demographic and clinicopathological factors. RESULTS: MSI status was available for 5,457 patients (609 MSI, 11.2%; 4848 microsatellite stable [MSS], 88.8%) from 12 randomized clinical trials (RCTs). Oxaliplatin significantly improved OS of MSI patients from the two RCTs testing FP with or without oxaliplatin (n = 185; adjusted hazard ratio [aHR] = 0.52, 95% CI, 0.28 to 0.93). Among the 4,250 patients treated with FP plus oxaliplatin (461 MSI and 3789 MSS), MSI was associated with better OS in the N1 group compared with MSS (aHR = 0.66; 95% CI, 0.46 to 0.95) but similar survival in the N2 population (aHR = 1.13; 95% CI, 0.86 to 1.48; P interaction = .029). The main independent prognosticators of MSI patients treated with FP plus oxaliplatin were T stage (aHR = 2.09; 95% CI, 1.29 to 3.38) and N stage (aHR = 3.57; 95% CI, 2.32 to 5.48). Similar results were observed for DFS in all analyses. CONCLUSION: Adding oxaliplatin to FP improves OS and DFS in patients with MSI stage III CC. Compared with MSS, MSI patients experienced better outcomes in the N1 group but similar survival in the N2 group.
PURPOSE: In patients with stage III colon cancer (CC) whose tumors demonstrate microsatellite instability (MSI), the efficacy of adjuvant fluoropyrimidine (FP) with or without oxaliplatin has not been clearly demonstrated and the prognostic value of MSI remains uncertain. MATERIALS AND METHODS: Individual patient data from the ACCENT database were used to evaluate the effect of FP with or without oxaliplatin on disease-free survival (DFS) and overall survival (OS) among patients with MSI stage III CC and the prognostic value of MSI in patients treated with FP plus oxaliplatin, by stratified Cox models adjusted for demographic and clinicopathological factors. RESULTS: MSI status was available for 5,457 patients (609 MSI, 11.2%; 4848 microsatellite stable [MSS], 88.8%) from 12 randomized clinical trials (RCTs). Oxaliplatin significantly improved OS of MSI patients from the two RCTs testing FP with or without oxaliplatin (n = 185; adjusted hazard ratio [aHR] = 0.52, 95% CI, 0.28 to 0.93). Among the 4,250 patients treated with FP plus oxaliplatin (461 MSI and 3789 MSS), MSI was associated with better OS in the N1 group compared with MSS (aHR = 0.66; 95% CI, 0.46 to 0.95) but similar survival in the N2 population (aHR = 1.13; 95% CI, 0.86 to 1.48; P interaction = .029). The main independent prognosticators of MSI patients treated with FP plus oxaliplatin were T stage (aHR = 2.09; 95% CI, 1.29 to 3.38) and N stage (aHR = 3.57; 95% CI, 2.32 to 5.48). Similar results were observed for DFS in all analyses. CONCLUSION: Adding oxaliplatin to FP improves OS and DFS in patients with MSI stage III CC. Compared with MSS, MSI patients experienced better outcomes in the N1 group but similar survival in the N2 group.
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