Efficacy and Safety of Bevacizumab in Metastatic Colorectal Cancer: Pooled Analysis From Seven Randomized Controlled Trials
Efficacy and Safety of Bevacizumab in Metastatic Colorectal Cancer: Pooled Analysis From Seven Randomized Controlled Trials
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DOI：
10.1634/theoncologist.2013-0107
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发表时间：
2013-09-01
期刊：
影响因子：
5.8
通讯作者：
Tabernero, Josep
中科院分区：
文献类型：
--
作者：
Hurwitz, Herbert I.;Tebbutt, Niall C.;Tabernero, Josep
目的.本分析汇集了来自随机对照试验（RCT）的个体患者数据，以更彻底地检查在转移性结直肠癌（mCRC）患者化疗中加入贝伐单抗的临床结局。汇总了来自一线AVF 2107、NO16966、ARTIST、AVF 0780、AVF 2192和AGITG MAX RCT以及二线E3200 RCT的患者数据。所有分析均基于意向治疗人群。为了评估不同治疗（化疗联合或不联合安慰剂与化疗联合贝伐单抗）的时间-事件变量差异，使用分层随机效应（总体）和固定效应（亚组比较）模型估计合并风险比（HR）和95%置信区间（CI）。分析人群包括3，763例患者（1，773例化疗加或不加安慰剂; 1，990例化疗加贝伐单抗）。在化疗基础上加用贝伐珠单抗与总生存期（OS; HR，0.80; 95%CI，0.71-0.90）和无进展生存期（PFS; HR，0.57; 95%CI，0.46 - 0.71）的统计学显著性增加相关。根据化疗基础（基于奥沙利铂，基于伊立替康）、疾病程度（仅肝转移，广泛性疾病）、年龄（≥ 65岁）、东部肿瘤协作组体能状态（0，>= 1）和KRAS状态（野生型，突变型）定义的亚组中对OS和PFS的影响与总体分析一致。贝伐单抗治疗后3级以上高血压、蛋白尿、出血、伤口愈合并发症、胃肠道穿孔和血栓栓塞事件的发生率增加。贝伐珠单抗联合化疗导致mCRC患者的OS和PFS统计学显著增加。PFS获益在检查的临床相关亚组中扩展。观察到的贝伐珠单抗安全性特征与个体试验中报告的一致。
Purpose. This analysis pooled individual patient data from randomized controlled trials (RCTs) tomorethoroughlyexamine clinical outcomes when adding bevacizumab to chemotherapy for patients with metastatic colorectal cancer (mCRC).Patients and Methods. Patient data were pooled from the first-line AVF2107, NO16966, ARTIST, AVF0780, AVF2192, and AGITG MAX RCTs and the second-line E3200 RCT. All analyses werebasedonthe intent-to-treat population. Toassess differences in time-to-event variables by treatment (chemotherapy with or without placebo vs. chemotherapy plus bevacizumab), stratified random-effects (overall) and fixed-effects (subgroup comparisons) models were used to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs).Results. The analysis population comprised 3,763 patients (1,773 chemotherapy with or without placebo; 1,990 chemotherapy plus bevacizumab). The addition of bevacizumab to chemotherapy was associated with statistically significant in-creases in overall survival (OS; HR, 0.80; 95% CI, 0.71-0.90) and progression-free survival (PFS; HR, 0.57; 95% CI, 0.46 0.71). The effects on OS and PFS across subgroups defined by chemotherapy backbone (oxaliplatin-based, irinotecan-based), extent of disease (liver metastases only, extensive disease), age (= 65 years), Eastern Cooperative Oncology Group performance status (0, >= 1), and KRAS status (wildtype, mutant) were consistent with the overall analysis. Incidence rates of grade >= 3 hypertension, proteinuria, bleeding, wound-healing complications, gastrointestinal perforations, and thromboembolic events were increased with bevacizumab treatment.Conclusion. The use of bevacizumab with chemotherapy resulted in statistically significant increases in OS and PFS for patients with mCRC. The PFS benefit extended across the clinically relevant subgroups examined. The observed safety profile of bevacizumab was consistent with that reported in individual trials.