University of Florida, Division of Hematology and Oncology, 1600 SW Archer Ave, Rm N-503, Gainesville, FL 32610, USA.
J Clin Oncol. 2013 Jan 20;31(3):359-64. doi: 10.1200/JCO.2012.44.4711. Epub 2012 Dec 10.
PURPOSE: The National Surgical Adjuvant Breast and Bowel Project trial C-08 was designed to investigate the safety and efficacy of adding bevacizumab to fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) for the adjuvant treatment of patients with stage 2-3 colon cancer. Our report summarizes the primary and secondary end points of disease-free and overall survival, respectively, with 5 years median follow-up time. PATIENTS AND METHODS: Patients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus bevacizumab (5 mg/kg) once every 2 weeks for a 12-month period (experimental group). The primary end point of the study was disease-free survival (DFS) and overall survival (OS) was a secondary end point. RESULTS: Of 2,673 analyzed patients, demographic factors were well-balanced by treatment. With a median follow-up of 5 years, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.93; 95% CI, 0.81 to 1.08; P = .35). Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 1.25-year landmark (time-by-treatment interaction P value <.0001). The secondary end point of OS was no different between the two study arms for all patients (HR, 0.95; 95% CI, 0.79 to 1.13; P = .56) and for those with stage 3 disease (HR, 1.0; 95% CI, 0.83 to 1.21; P = .99). CONCLUSION: Bevacizumab for 1 year with modified FOLFOX6 does not significantly prolong DFS or OS in stage 2-3 colon cancer. We observed no evidence of a detrimental effect of exposure to bevacizumab. A transient effect on disease-free survival was observed during bevacizumab exposure in the study's experimental arm.
目的:国家外科辅助乳腺和肠道项目试验 C-08 旨在研究贝伐单抗联合氟尿嘧啶、亚叶酸钙和奥沙利铂(FOLFOX6)用于辅助治疗 2-3 期结肠癌患者的安全性和疗效。我们的报告总结了疾病无进展和总生存的主要和次要终点,中位随访时间为 5 年。
患者和方法:患者接受每 2 周一次的改良 FOLFOX6 治疗 6 个月(对照组)或改良 FOLFOX6 治疗 6 个月加贝伐单抗(5mg/kg)每 2 周一次治疗 12 个月(实验组)。该研究的主要终点是无病生存(DFS),总生存(OS)是次要终点。
结果:在 2673 例分析患者中,治疗组的人口统计学因素均衡。中位随访 5 年后,贝伐单抗联合 mFOLFOX6 治疗并未显著增加总生存(风险比[HR],0.93;95%置信区间,0.81 至 1.08;P=.35)。探索性分析发现,贝伐单抗对 DFS 的影响在 1.25 年里程碑前后不同(时间与治疗的交互作用 P 值<.0001)。在所有患者和 3 期疾病患者中,两组间的次要终点 OS 无差异(HR,0.95;95%置信区间,0.79 至 1.13;P=.56)。
结论:改良 FOLFOX6 联合贝伐单抗治疗 1 年并未显著延长 2-3 期结肠癌患者的 DFS 或 OS。我们没有观察到暴露于贝伐单抗有不良影响的证据。在研究的实验组中,贝伐单抗暴露期间观察到疾病无进展生存的短暂影响。
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