年龄对奥沙利铂在直肠癌术前放化疗和辅助化疗中的疗效的影响：CAO/ARO/AIO-04 三期临床试验的事后分析。
Impact of age on the efficacy of oxaliplatin in the preoperative chemoradiotherapy and adjuvant chemotherapy of rectal cancer: a post hoc analysis of the CAO/ARO/AIO-04 phase III trial.
机构信息
Interdisciplinary Tumor Center, University Hospital Mannheim, University of Heidelberg, Heidelberg, Germany.
Department of Oncology and Hematology, Asklepios Clinic Altona, Hamburg, Germany.
出版信息
Ann Oncol. 2018 Aug 1;29(8):1793-1799. doi: 10.1093/annonc/mdy205.
BACKGROUND
The German rectal cancer trial CAO/ARO/AIO-04 has shown a significant benefit in 3-year disease-free survival (DFS) of adding oxaliplatin to a standard preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) and adjuvant chemotherapy in patients with locally advanced rectal cancer. The use of oxaliplatin as adjuvant treatment in elderly patients with colon cancer is controversial. We therefore investigated the impact of age on clinical outcome in the CAO/ARO/AIO-04 phase III trial.
PATIENTS AND METHODS
We carried out a post hoc analysis of the CAO/ARO/AIO-04 phase III trial evaluating primary and secondary end points according to age. Patient and tumor characteristics, NCI CTC adverse events grades 3-4 (version 3.0), dose intensities as well as survival and recurrence data were analyzed in three specified age groups (<60, 60-70, and ≥70 years). The influence of age as a continuous variable on DFS was modeled using a subpopulation treatment effect pattern plot (STEPP) analysis.
RESULTS
A total of 1232 patients were assessable. With the exception of Eastern Cooperative Oncology Group status (P < 0.001), no differences in patient and tumor characteristics were noticed between age groups. Likewise, toxicity pattern, dose intensities of CRT and surgical results were similar in all age groups. After a median follow-up of 50 months, in patients aged <60 years a significant benefit of adding oxaliplatin to 5-FU-based CRT and adjuvant chemotherapy was observed for local (P = 0.013) and systemic recurrences (P = 0.023), DFS (P = 0.011), and even overall survival (OS; P = 0.044). The STEPP analysis revealed improved hazard ratios for DFS in patients aged 40-70 years compared with elderly patients treated with oxaliplatin.
CONCLUSION
The addition of oxaliplatin significantly improved DFS and OS in younger patients aged <60 years with advanced rectal cancer. Patients aged ≥70 years had no benefit.
CLINICAL TRIALS NUMBER
NCT00349076.
背景
德国直肠癌试验 CAO/ARO/AIO-04 表明，在局部晚期直肠癌患者中，奥沙利铂联合标准术前氟尿嘧啶（5-FU）为基础的放化疗（CRT）和辅助化疗可显著提高 3 年无病生存率（DFS）。奥沙利铂作为老年结肠癌辅助治疗的应用存在争议。因此，我们在 CAO/ARO/AIO-04 期临床试验中研究了年龄对临床结局的影响。
方法
我们对 CAO/ARO/AIO-04 期临床试验进行了事后分析，根据年龄评估了主要和次要终点。分析了患者和肿瘤特征、NCI CTC 不良事件 3-4 级（第 3.0 版）、剂量强度以及生存和复发数据，分为 3 个特定年龄组（<60 岁、60-70 岁和≥70 岁）。使用亚组治疗效果模式图（STEPP）分析评估年龄作为连续变量对 DFS 的影响。
结果
共 1232 例患者可评估。除东部肿瘤协作组（ECOG）状态外（P<0.001），不同年龄组之间的患者和肿瘤特征无差异。同样，在所有年龄组中，毒性模式、CRT 和手术结果的剂量强度均相似。中位随访 50 个月后，在<60 岁的患者中，奥沙利铂联合 5-FU 为基础的 CRT 和辅助化疗显著降低了局部（P=0.013）和全身复发（P=0.023）、DFS（P=0.011）甚至总生存（OS；P=0.044）的风险。STEPP 分析显示，40-70 岁年龄组患者的 DFS 风险比与接受奥沙利铂治疗的老年患者相比有所改善。
结论
在年龄<60 岁的晚期直肠癌患者中，奥沙利铂的加入显著提高了 DFS 和 OS，而年龄≥70 岁的患者则无获益。
临床试验编号
NCT00349076。
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