Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials

Author:

Cohen Romain12ORCID,Taieb Julien3ORCID,Fiskum Jack2,Yothers Greg4,Goldberg Richard5ORCID,Yoshino Takayuki6ORCID,Alberts Steven7ORCID,Allegra Carmen8,de Gramont Aimery9,Seitz Jean-Francois10,O'Connell Michael7,Haller Daniel11,Wolmark Norman12,Erlichman Charles7,Zaniboni Alberto13,Lonardi Sara14ORCID,Kerr Rachel15,Grothey Axel16,Sinicrope Frank A.7ORCID,André Thierry1ORCID,Shi Qian2ORCID

Affiliation:

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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3