METHODS: Patients were included from three prospective trials of ICI (pembrolizumab; nivolumab/urelumab or nivolumab/cabiralizumab; nivolumab/ipilimumab) with SBRT to 1-4 sites. AEs were recorded prospectively using the CTCAE v4.0. Survival was analyzed using Kaplan-Meier method with a 90-day landmark. Association of patient characteristics with cumulative incidence of AEs was assessed using Fine-Gray regression.
RESULTS: 213 patients were included, with a median follow-up of 10 months. Over the follow-up period, 50 % and 27 % of patients experienced at least one grade ≥ 2 or grade ≥ 3 AE, respectively. Cumulative incidences of grade ≥ 2 and grade ≥ 3 AEs at 6 months were 47 % and 23 %, respectively. Three grade 5 AEs rated \"possibly\" related to treatment occurred outside the 90-day dose-limiting toxicity window. Landmarked survival analysis of patients with or without grade ≥ 3 AEs showed no significant difference in progression-free or overall survival. Dual-agent ICI was significantly associated with grade ≥ 3 AE.
CONCLUSIONS: This analysis features the largest prospectively evaluated cohort of patients treated with combination ablative SBRT and ICI to date and provides context for future trial design. We conclude that multi-site SBRT and ICI can be safely co-administered when SBRT is delivered with prioritization of normal tissue constraints.
方法:患者纳入了3项ICI前瞻性试验(pembrolizumab;nivolumab/urelumab或nivolumab/cabiralizumab;nivolumab/ipilimumab),SBRT至1-4个位点。使用CTCAEv4.0前瞻性记录AE。使用具有90天标志的Kaplan-Meier方法分析存活。使用Fine-Gray回归评估患者特征与AE累积发生率的关联。
结果:纳入213例患者,中位随访时间为10个月。在随访期间,50%和27%的患者经历至少一个≥2级或≥3级AE,分别。6个月≥2级和≥3级不良事件的累积发生率分别为47%和23%,分别。在90天剂量限制性毒性窗口之外发生了与治疗相关的“可能”等级5级AE。有或没有≥3级AEs的患者的标志生存分析显示,无进展生存或总生存没有显着差异。双药ICI与≥3级AE显著相关。
结论:本分析的特点是迄今为止最大的前瞻性评估队列患者接受消融性SBRT和ICI联合治疗,并为未来的试验设计提供了背景。我们得出的结论是,在优先考虑正常组织约束的情况下交付SBRT时,可以安全地共同施用多位点SBRT和ICI。