Mount Vernon Cancer Centre, Rickmansworth Rd, Northwood, London HA6 2RN, United Kingdom.
J Clin Oncol. 2011 Jan 1;29(1):83-8. doi: 10.1200/JCO.2010.30.2794. Epub 2010 Nov 22.
Preclinical studies have suggested accelerated tumor growth, local invasion, and distant metastasis after withdrawal of treatment with some antiangiogenic agents. To investigate whether discontinuation of bevacizumab treatment is associated with accelerated disease progression or increased mortality, we retrospectively analyzed five randomized, placebo-controlled phase III studies in 4,205 patients with breast, colorectal, renal, and pancreatic cancer.
Time from treatment discontinuation to progressive disease or death was analyzed in patients discontinuing bevacizumab/placebo as a result of adverse events (AEs). Mortality rates were assessed at 30, 60, 90, 120, 150, 180, and 210 days after the last bevacizumab/placebo dose in the following two groups: patients discontinuing bevacizumab/placebo as a result of AEs and patients discontinuing bevacizumab/placebo for any reason. In the same groups, time from treatment discontinuation to death was analyzed. Data on disease progression pattern were available and analyzed in four of the five studies.
In the pooled analysis, median time from discontinuation as a result of AEs to progression/death was 3.0 months (95% CI, 2.6 to 3.8 months) for placebo and 4.0 months (95% CI, 3.4 to 4.6 months) for bevacizumab (hazard ratio, 0.93; 95% CI, 0.79 to 1.10). Mortality rates from 30 days to 210 days after treatment discontinuation and time from discontinuation to death were similar in bevacizumab- and placebo-treated patients. In addition, similar patterns of disease progression were seen in bevacizumab- and placebo-treated patients.
This retrospective analysis of five placebo-controlled clinical trials does not support a decreased time to disease progression, increased mortality, or altered disease progression pattern after cessation of bevacizumab therapy.
临床前研究表明，在停止使用某些抗血管生成药物后，肿瘤生长、局部侵袭和远处转移会加速。为了研究贝伐珠单抗治疗停药后是否与疾病进展加速或死亡率增加有关，我们对 4205 例患有乳腺癌、结直肠癌、肾癌和胰腺癌的患者进行的五项随机、安慰剂对照 III 期研究进行了回顾性分析。
对因不良事件（AE）而停用贝伐珠单抗/安慰剂的患者，从治疗停药到疾病进展或死亡的时间进行了分析。在以下两组中评估了 30、60、90、120、150、180 和 210 天后最后一次贝伐珠单抗/安慰剂剂量的死亡率：因 AE 而停用贝伐珠单抗/安慰剂的患者和因任何原因停用贝伐珠单抗/安慰剂的患者。在相同的组中，从治疗停药到死亡的时间进行了分析。五项研究中的四项提供了疾病进展模式的数据并进行了分析。
在汇总分析中，因 AE 而停药后进展/死亡的中位时间为安慰剂组 3.0 个月（95%CI，2.6 至 3.8 个月）和贝伐珠单抗组 4.0 个月（95%CI，3.4 至 4.6 个月）（风险比，0.93；95%CI，0.79 至 1.10）。贝伐珠单抗和安慰剂治疗患者从治疗停药后 30 天至 210 天的死亡率以及从停药到死亡的时间相似。此外，贝伐珠单抗和安慰剂治疗患者的疾病进展模式相似。
这项对五项安慰剂对照临床试验的回顾性分析不支持贝伐珠单抗治疗停药后疾病进展时间缩短、死亡率增加或疾病进展模式改变。
