局部原发肿瘤的定位和 RAS/BRAF 突变状态对转移性结直肠癌一线奥沙利铂、氟嘧啶和贝伐珠单抗治疗后维持策略的影响：来自 AIO 0207 试验的结果。

Impact of the Localization of the Primary Tumor and RAS/BRAF Mutational Status on Maintenance Strategies After First-line Oxaliplatin, Fluoropyrimidine, and Bevacizumab in Metastatic Colorectal Cancer: Results From the AIO 0207 Trial.

机构信息

Division of Hematology, Oncology and Palliative Care, St. Josef-Hospital Bochum, Ruhr-University, Bochum, Germany.

Asklepiostumorzentrum Hamburg, Department of Oncology and Hematology, Palliative Care, AK Altona, Hamburg, Germany.

出版信息

Clin Colorectal Cancer. 2018 Dec;17(4):e733-e739. doi: 10.1016/j.clcc.2018.07.007. Epub 2018 Jul 25.

DOI:10.1016/j.clcc.2018.07.007

PMID:30145148

Abstract

INTRODUCTION

Numerous trials have examined the prognostic and predictive value of localization of the primary tumor (LPT) in metastastic colorectal cancer, there is limited information about the predictive value of LPT on different maintenance strategies.

MATERIALS AND METHODS

We analyzed progression-free survival (PFS)/overall survival (OS) on maintenance therapy according to LPT and mutational subgroups (BRAF/RAS) in patients from the AIO (Arbeitsgemeinschaft Internistische Onkologie) 0207 trial. Following induction, 471 patients were randomized to fluoropyrimidine (FU)/bevacizumab (Bev), Bev, or no treatment. Data on LPT were available in 414 (91%) patients.

RESULTS

A total of 291 patients were left-sided (LPTl, 70%), and 123 were right-sided (LPTr, 30%). The median PFS was 3.9 months for LPTr and 5.3 months for LPTl (P = .11; hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.96-1.48). There was no predictive impact of LPT on the maintenance strategies. The pairwise comparison of treatment arms showed a better PFS for FU/Bev versus no treatment independent from LPT (left, P < .0001; HR, 2.39; 95% CI, 1.73-3.31; right, P = .011; HR, 1.78; 95% CI, 1.14-2.80). Analysis for OS (429 patients) confirmed the strong prognostic impact of LPT (left vs. right: 24.0 vs. 16.7 months; P < .0001; HR, 1.65; 95% CI, 1.32-2.06), but also without major interaction between the LPT and maintenance arms. The strong negative prognostic impact of BRAF mutation was confirmed in right-/left-sided metastastic colorectal cancer, reaching significance in LPTl. In patients with RAS mutational status, the negative prognostic impact of the mutation remains, but its effect is stronger in LPTl (P < .0001).

CONCLUSION

The strong prognostic factor of LPT is confirmed undergoing oxaliplatin/FU/Bev induction therapy, whereas there seems to be no major predictive impact of LPT on different maintenance strategies.

摘要

介绍

大量试验已经研究了转移性结直肠癌中原发肿瘤定位（LPT）的预后和预测价值，但关于 LPT 对不同维持策略的预测价值的信息有限。

材料和方法

我们根据 AIO（德国内科肿瘤学会）0207 试验中 LPT 和突变亚组（BRAF/RAS）分析了维持治疗的无进展生存期（PFS）/总生存期（OS）。在诱导后，471 名患者被随机分配接受氟嘧啶（FU）/贝伐珠单抗（Bev）、Bev 或不治疗。414 名（91%）患者有 LPT 数据。

结果

共有 291 名患者为左侧（LPTl，70%），123 名患者为右侧（LPTr，30%）。LPTr 的中位 PFS 为 3.9 个月，LPTl 为 5.3 个月（P=0.11；风险比[HR]，1.19；95%置信区间[CI]，0.96-1.48）。LPT 对维持策略没有预测影响。治疗臂的两两比较显示，FU/Bev 与不治疗相比，无论 LPT 如何，PFS 均更好（左侧，P<0.0001；HR，2.39；95%CI，1.73-3.31；右侧，P=0.011；HR，1.78；95%CI，1.14-2.80）。OS（429 名患者）分析证实了 LPT 的强烈预后影响（左侧 vs. 右侧：24.0 个月 vs. 16.7 个月；P<0.0001；HR，1.65；95%CI，1.32-2.06），但 LPT 和维持臂之间也没有主要的相互作用。BRAF 突变的强烈负预后影响在右侧/左侧转移性结直肠癌中得到证实，在 LPTl 中达到显著水平。在 RAS 突变状态的患者中，突变的负预后影响仍然存在，但在 LPTl 中更强（P<0.0001）。