NRG Oncology/RTOG1205：贝伐珠单抗联合再放疗与贝伐珠单抗单药治疗复发性胶质母细胞瘤的随机 II 期试验。
NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma.
机构信息
Johns Hopkins School of Medicine, Baltimore, MD.
NRG Oncology Statistics and Data Management Center, Philadelphia, PA.
出版信息
J Clin Oncol. 2023 Feb 20;41(6):1285-1295. doi: 10.1200/JCO.22.00164. Epub 2022 Oct 19.
PURPOSE
To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities.
METHODS
NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone. Stratification factors included age, resection, and Karnofsky performance status (KPS). Patients with recurrent GBM with imaging evidence of tumor progression ≥ 6 months from completion of prior chemo-RT were eligible. Patients were randomly assigned 1:1 to re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once in every 2 weeks or BEV alone until progression.
RESULTS
From December 2012 to April 2016, 182 patients were randomly assigned, of whom 170 were eligible. Patient characteristics were well balanced between arms. The median follow-up for censored patients was 12.8 months. There was no improvement in OS for BEV + RT, hazard ratio, 0.98; 80% CI, 0.79 to 1.23; = .46; the median survival time was 10.1 versus 9.7 months for BEV + RT versus BEV alone. The median PFS for BEV + RT was 7.1 versus 3.8 months for BEV, hazard ratio, 0.73; 95% CI, 0.53 to 1.0; = .05. The 6-month PFS rate improved from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1) for BEV + RT, = .001. Treatment was well tolerated. There were a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs. Most patients died of recurrent GBM.
CONCLUSION
To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of re-RT in recurrent GBM using modern RT techniques. Overall, re-RT was shown to be safe and well tolerated. BEV + RT demonstrated a clinically meaningful improvement in PFS, specifically the 6-month PFS rate but no difference in OS.
目的
评估复发性胶质母细胞瘤（GBM）中再放疗（re-RT）和贝伐单抗（BEV）联合治疗与单独使用 BEV 相比，是否能改善总生存期（OS）和/或无进展生存期（PFS）。主要研究目标为 OS，次要研究目标包括 PFS、缓解率以及包括迟发性中枢神经系统毒性在内的治疗不良事件（AEs）。
方法
NRG 肿瘤学/RTOG1205 是一项前瞻性、二期、随机试验，评估了再放疗和 BEV 联合治疗与单独使用 BEV 治疗复发性 GBM 的效果。分层因素包括年龄、切除程度和卡氏功能状态评分（KPS）。有影像学证据显示在完成先前的化疗-放疗后肿瘤进展≥6 个月的复发性 GBM 患者符合入组条件。患者随机以 1:1 的比例分配至 re-RT 组或 BEV 组。re-RT 组接受 35 Gy/10 次分割放疗，同时静脉给予 10 mg/kg 的 BEV，每 2 周一次；BEV 组单独使用 BEV 直至疾病进展。
结果
2012 年 12 月至 2016 年 4 月期间，共随机分配了 182 例患者，其中 170 例患者符合条件。两组患者的特征在各亚组间均衡可比。对于删失患者，中位随访时间为 12.8 个月。与单独使用 BEV 相比，BEV+RT 并未改善 OS，风险比为 0.98；95%CI，0.79 至 1.23；P=0.46；BEV+RT 组和 BEV 组的中位生存时间分别为 10.1 个月和 9.7 个月。BEV+RT 组和 BEV 组的中位 PFS 分别为 7.1 个月和 3.8 个月，风险比为 0.73；95%CI，0.53 至 1.0；P=0.05。与单独使用 BEV 相比，BEV+RT 治疗使 6 个月时的 PFS 率从 29.1%（95%CI，19.1 至 39.1）提高到 54.3%（95%CI，43.5 至 65.1），P=0.001。治疗耐受性良好。急性 3+级治疗相关 AEs 的发生率为 5%，无迟发性高级别 AEs。大多数患者死于复发性 GBM。
结论
据我们所知，NRG 肿瘤学/RTOG1205 是第一项前瞻性、随机、多中心研究，评估了使用现代放疗技术治疗复发性 GBM 时再放疗的安全性和有效性。总的来说，再放疗是安全且耐受良好的。与单独使用 BEV 相比，BEV+RT 可显著改善 PFS，尤其是 6 个月时的 PFS 率，但 OS 无差异。
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