粒细胞集落刺激因子或培非格司亭对接受骨髓抑制性化疗的癌症患者生存结局的影响。

The effect of filgrastim or pegfilgrastim on survival outcomes of patients with cancer receiving myelosuppressive chemotherapy.

机构信息

Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center and the Department of Medicine, University of Washington, Seattle

Global Biostatistical Science, Amgen Inc., Thousand Oaks.

出版信息

Ann Oncol. 2015 Jul;26(7):1452-8. doi: 10.1093/annonc/mdv174. Epub 2015 Apr 7.

DOI:10.1093/annonc/mdv174

PMID:25851633

Abstract

BACKGROUND

Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is associated with higher chemotherapy relative dose intensity, which may lead to improved outcomes; however, the association between G-CSF primary prophylaxis and overall survival (OS) is not well characterized. This study assessed the effect of G-CSF primary prophylaxis on patient outcomes in randomized, controlled, registrational clinical trials of filgrastim and pegfilgrastim.

PATIENTS AND METHODS

Three placebo-controlled and two non-inferiority clinical trials of filgrastim and/or pegfilgrastim in patients receiving myelosuppressive chemotherapy for lung, breast, or colorectal cancer were included. The median OS, 6- and 12-month survival rates, and hazard ratios [HRs; unadjusted Cox model with 95% confidence intervals (CIs)] were estimated for patients receiving ≥1 dose of filgrastim, pegfilgrastim, or placebo. Comparisons were based on a log-rank test. A fixed-effect meta-analysis assessed the effect of primary prophylaxis with filgrastim/pegfilgrastim on OS in the placebo-controlled trials.

RESULTS

In patients with lung cancer receiving filgrastim versus placebo, the median OS was 14.1 versus 11.1 months (HR, 0.81; 95% CI 0.48-1.35; P = 0.412); in patients who crossed over to filgrastim from placebo after cycle 1, the median OS was 16.9 months (HR, 0.75; 95% CI 0.43-1.28; P = 0.286). The median OS was inestimable in at least one treatment arm in the other studies because of the small number of OS events. Where estimable, 6- and 12-month survival rates were generally greater among patients receiving filgrastim/pegfilgrastim versus placebo. In the meta-analysis of placebo-controlled studies comparing G-CSF primary prophylaxis with placebo in the as-treated analysis sets, the HR (95% CI) for OS was 0.77 (0.58-1.03).

CONCLUSIONS

In this retrospective analysis, OS point estimates were greater among patients receiving filgrastim versus placebo, but the differences were not statistically significant. Further studies evaluating patient outcomes with G-CSF prophylaxis are warranted.

CLINICAL TRIAL REGISTRATION

NCT00035594, NCT00094809.

摘要

背景

粒细胞集落刺激因子（G-CSF）的初级预防与更高的化疗相对剂量强度相关，这可能导致更好的结果；然而，G-CSF 初级预防与总生存（OS）之间的关系尚未得到很好的描述。本研究评估了粒细胞集落刺激因子初级预防对接受粒细胞集落刺激因子治疗的肺、乳腺或结直肠癌症患者随机对照注册临床试验中患者结局的影响。

患者和方法

纳入了三项培非格司亭和 pegfilgrastim 的安慰剂对照临床试验，以及两项非劣效性临床试验，用于接受骨髓抑制化疗的肺、乳腺或结直肠癌症患者。对接受培非格司亭、pegfilgrastim 或安慰剂的患者进行了中位 OS、6 个月和 12 个月的生存率以及风险比（HR；未调整的 Cox 模型，置信区间 [CI] 为 95%）的估计。比较基于对数秩检验。固定效应荟萃分析评估了培非格司亭/pegfilgrastim 初级预防对安慰剂对照试验中 OS 的影响。

结果

在接受培非格司亭治疗的肺癌患者中，中位 OS 为 14.1 个月，而安慰剂组为 11.1 个月（HR，0.81；95%CI，0.48-1.35；P=0.412）；在第 1 周期后从安慰剂交叉至培非格司亭的患者中，中位 OS 为 16.9 个月（HR，0.75；95%CI，0.43-1.28；P=0.286）。由于 OS 事件数量较少，其他研究中至少有一个治疗组的中位 OS 无法估计。在可估计的情况下，接受培非格司亭/pegfilgrastim 治疗的患者的 6 个月和 12 个月生存率通常高于安慰剂组。在按治疗意向治疗分析集比较 G-CSF 初级预防与安慰剂的安慰剂对照研究的荟萃分析中，OS 的 HR（95%CI）为 0.77（0.58-1.03）。