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一线使用贝伐单抗可能会延长未接受二线治疗的胶质母细胞瘤患者的生存期:AVAglio研究的探索性分析

Upfront bevacizumab may extend survival for glioblastoma patients who do not receive second-line therapy: an exploratory analysis of AVAglio.

作者信息

Chinot Olivier L, Nishikawa Ryo, Mason Warren, Henriksson Roger, Saran Frank, Cloughesy Timothy, Garcia Josep, Revil Cedric, Abrey Lauren, Wick Wolfgang

机构信息

Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); Princess Margaret Hospital, Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.)

Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); Princess Margaret Hospital, Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.).

出版信息

Neuro Oncol. 2016 Sep;18(9):1313-8. doi: 10.1093/neuonc/now046. Epub 2016 Mar 22.

Abstract

BACKGROUND

In this post-hoc, exploratory analysis, we examined outcomes for patients enrolled in the AVAglio trial of front-line bevacizumab or placebo plus radiotherapy/temozolomide who received only a single line of therapy.

METHODS

Patients with newly diagnosed glioblastoma received protocol-defined treatment until progressive disease (PD). Co-primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). After confirmed PD, patients were treated at the investigators' discretion. PFS/OS were assessed in patients with a PFS event who did not receive post-PD therapy (Group 1) and patients with a PFS event who received post-PD therapy plus patients who did not have a PFS event at the final data cutoff (Group 2). Kaplan-Meier methodology was used. A multivariate Cox proportional hazards model for known prognostic variables was generated.

RESULTS

Baseline characteristics were balanced. In patients with a PFS event who did not receive post-PD therapy (Group 1; n = 225 [24.4% of the intent-to-treat population]), the addition of bevacizumab to radiotherapy/temozolomide resulted in a 3.6-month extension in both median PFS (hazard ratio [HR]: 0.62, P = .0016) and median OS (HR: 0.67, P = .0102). Multivariate analyses supported this OS benefit (HR: 0.66). In the remaining patients (Group 2; n = 696), a 5.2-month PFS extension was observed in bevacizumab-treated patients (HR: 0.61, P < .0001); OS was comparable between the treatment arms (HR: 0.88, P = .1502). No significant differences in safety were observed between the 2 groups.

CONCLUSION

This exploratory analysis suggests that the addition of bevacizumab to standard glioblastoma treatment prolongs PFS and OS for patients with PD who receive only one line of therapy.

摘要

背景

在这项事后探索性分析中,我们研究了仅接受一线治疗的、参加阿伐单抗一线治疗联合放疗/替莫唑胺或安慰剂对照试验的患者的预后情况。

方法

新诊断的胶质母细胞瘤患者接受方案定义的治疗,直至疾病进展(PD)。共同主要终点为研究者评估的无进展生存期(PFS)和总生存期(OS)。确诊为PD后,患者由研究者酌情治疗。对发生PFS事件但未接受PD后治疗的患者(第1组)以及发生PFS事件且接受PD后治疗的患者加上在最终数据截止时未发生PFS事件的患者(第2组)进行PFS/OS评估。采用Kaplan-Meier方法。针对已知预后变量生成多变量Cox比例风险模型。

结果

基线特征均衡。在发生PFS事件但未接受PD后治疗的患者(第1组;n = 225 [意向性治疗人群的24.4%])中,放疗/替莫唑胺联合使用阿伐单抗使中位PFS延长3.6个月(风险比[HR]:0.62,P = 0.0016),中位OS延长3.6个月(HR:0.67,P = 0.0102)。多变量分析支持这一OS获益(HR:0.66)。在其余患者(第2组;n = 696)中,阿伐单抗治疗的患者PFS延长5.2个月(HR:0.61,P < 0.0001);各治疗组之间OS相当(HR:0.88,P = 0.1502)。两组之间在安全性方面未观察到显著差异。

结论

这项探索性分析表明,对于仅接受一线治疗的PD患者,在标准胶质母细胞瘤治疗中添加阿伐单抗可延长PFS和OS。

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