Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials
Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials
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DOI：
10.1200/jco.20.01600
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发表时间：
2021-02-20
影响因子：
45.3
通讯作者：
Shi, Qian
中科院分区：
文献类型：
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作者：
Cohen, Romain;Taieb, Julien;Shi, Qian
在肿瘤表现出微卫星不稳定性（MSI）的III期结肠癌（CC）患者中，辅助氟嘧啶（FP）与或不与奥沙利铂的疗效尚未得到明确证明，MSI的预后价值仍然不确定。材料和方法来自ACCENT数据库的个体患者数据用于评价FP与或不与奥沙利铂对无病生存（DFS）的影响。通过调整人口统计学和临床病理学因素的分层考克斯模型，对MSI III期CC患者的生存率和总生存率（OS）以及FP联合奥沙利铂治疗患者MSI的预后价值进行了研究。（609 MSI，11.2%; 4848微卫星稳定[MSS]，88.8%）来自12个随机临床试验（RCT）。奥沙利铂显著改善了来自两项RCT的MSI患者的OS，这些RCT检测FP联合或不联合奥沙利铂（n = 185;校正风险比[aHR] = 0. 52，95% CI，0. 28 - 0. 93）。在接受FP+奥沙利铂治疗的4,250例患者中（461例MSI和3789例MSS），与MSS相比，MSI与N1组更好的OS相关（aHR = 0.66; 95% CI，0.46 - 0.95），但与N2人群相似的生存率（aHR = 1.13; 95% CI，0.86 - 1.48; P相互作用= 0.029）。FP联合奥沙利铂治疗MSI患者的主要独立危险因素为T分期（aHR = 2.09; 95%CI，1.29 ~ 3.38）和N分期（aHR = 3.57; 95%CI，2.32 ~ 5.48）。结论FP加奥沙利铂可改善MSI III期CC患者的OS和DFS。与MSS相比，MSI患者在N1组中的结局更好，但在N2组中的生存率相似。(C)2020年美国临床肿瘤学会
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; Pinteraction = .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. (C) 2020 by American Society of Clinical Oncology