A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer
A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer
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DOI：
10.1016/j.ejca.2015.07.035
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发表时间：
2015-11-01
影响因子：
8.4
通讯作者：
Fakhrai, H.
中科院分区：
文献类型：
--
作者：
Giaccone, G.;Bazhenova, L. A.;Fakhrai, H.
背景：非小细胞肺癌（NSCLC）一线化疗后的治疗选择是有限的。Belagenpumatucel-L是一种治疗性疫苗，由4种转化生长因子(TGF)- β 2-反义基因修饰、辐照的异基因非小细胞肺癌细胞系组成，可能有助于初始治疗后的维持。方法：在铂类化疗后未进展的III/IV期NSCLC患者按1:1随机分组，接受维持治疗的belagenpumatucel-L或安慰剂。患者在诱导化疗结束后1 - 4个月内随机分组。主要终点是总生存期。结果：这项III期试验在belagenpumatucel-L组招募了270名患者，在对照组招募了262名患者。Belagenpumatucel-L耐受性良好，没有严重的安全问题。两组间的生存期无差异（中位生存期分别为20.3个月和17.8个月，风险比（HR） 0.94, p = 0.594）。两组无进展生存期也无差异（分别为4.3个月和4.0个月，HR 0.99, p = 0.947）。预先指定的Cox回归分析表明，随机化和诱导化疗结束之间的时间对生存有显著影响（p = 0.002），先前的放疗是一个积极的预后因素（belagenpumatucel-L组中位生存期28.4个月，安慰剂组中位生存期16.0个月；HR 0.61, p = 0.032）。结论：尽管总体试验没有达到其生存终点，但在化疗完成后12周内随机分组的患者和先前接受过放疗的患者中，belagenpumatucel-L的生存率得到了改善。需要进一步研究belagenpumatucel-L在NSCLC中的作用。(C) 2015年Elsevier Ltd.出版
Background: Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-beta 2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment.Methods: Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival.Results: This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8 months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p = 0.594). There were also no differences in progression-free survival (4.3 months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p = 0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p = 0.002) and that prior radiation was a positive prognostic factor (median survival 28.4 months with belagenpumatucel-L versus 16.0 months with placebo; HR 0.61, p = 0.032).Conclusions: Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12 weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted. (C) 2015 Published by Elsevier Ltd.