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标准一线放化疗方案中使用nivolumab联合同步放疗治疗iii期非小细胞肺癌的安全性评估—etop nicolas试验-ag捕鱼平台

文字: 2019-12-17    浏览次数:768    

objectives: chemo-radiotherapy (crt) and concurrent pd-1 inhibition has shown promising results in pre-clinical models. so far, the feasibility of delivering concurrent crt and pd-1/pd-l1 inhibition has never been assessed in a clinical trial.

目的pd-1抑制剂联合同步放化疗(crt)在临床前模型中显示出良好的结果。迄今为止,尚未在临床试验中评估pd-1/pd-l1抑制剂联合crt治疗的可行性。

 

material and methods: nicolas is a phase-ii trial evaluating the safety and efficacy of nivolumab combined with crt in stage iii nsclc. patients received 3 cycles of platinum-based chemotherapy and concurrent rt (66gy/33fractions). nivolumab started concurrently with rt. the primary endpoint was 6-month post-rt rate of grade-3-pneumonitis. a formal interim safety analysis (ia) was scheduled when the first 21 patients reached 3 months follow-up post-rt. an early positive safety conclusion would be reached at ia if there were no grade ≥3-pneumonitis in those patients. efficacy evaluation was planned provided the safety conclusion was reached.

材料与方法nicolas是一项ii期临床试验,旨在评估nivolumab联合crt治疗iiinsclc的安全性和有效性。患者接受3个周期的铂类化疗和同步rt (66 gy/33次完成)nivolumabrt同步开始,主要终点为rt 6个月后≥3级肺炎的发生率。前21例完成rt3个月随访的患者被安排进行一项正式的中期安全分析(ia)。如果这些患者中没有出现≥3级肺炎,则ia可得出早期阳性安全性结论。在得出安全性结论的前提下,进行疗效评价。

 

results and conclusion: as of 13 december 2018, 82 patients were recruited with median follow-up of 13.4 months. the most frequent adverse events (aes) were anaemia, fatigue and pneumonitis. no unexpected aes or increased toxicities were observed. for the first 21 patients, no grade-≥3-pneumonitis was observed by the end of the 3-month post-rt follow-up period. the early safety ia provides evidence that the addition of nivolumab to concurrent crt is safe and tolerable regarding the 6-month rate of pneumonitis grade ≥3 at the one-sided significance level of 5%. following that, the 1-year progression-free survival will be evaluated in an expanded patient cohort. nicolas trial creates the opportunity for assessing the activity of the combination of checkpoint with concurrent crt in larger prospective trials for locally advanced nsclc.

 

结果与结论:截至20181213日,共入组82例患者,中位随访时间13.4个月。最常见的不良事件(aes)是贫血、疲劳和肺炎。未观察到预料之外的aes或毒性增加现象。对于上述前21例患者,在rt3个月的随访结束时未观察到≥3级肺炎。早期安全性ia所提供的证据表明,nivolumab联合同步crt治疗6个月的3级肺炎发生率在单侧显著性检验水平5%时是安全且可耐受的。在此之后,将在更大的患者队列中评估1年的无进展生存期。nicolas试验为在更大规模的前瞻性试验中评估免疫检查点联合crt治疗局部晚期nsclc创造了的机会。