Progression-Free and Overall Survival for Concurrent Nivolumab With Standard Concurrent Chemoradiotherapy in Locally Advanced Stage IIIA-B NSCLC: Results From the European Thoracic Oncology Platform NICOLAS Phase II Trial (European Thoracic Oncology Platform 6-14)
Progression-Free and Overall Survival for Concurrent Nivolumab With Standard Concurrent Chemoradiotherapy in Locally Advanced Stage IIIA-B NSCLC: Results From the European Thoracic Oncology Platform NICOLAS Phase II Trial (European Thoracic Oncology Platform 6-14)
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DOI：
10.1016/j.jtho.2020.10.129
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发表时间：
2021-01-22
影响因子：
20.4
通讯作者：
De Ruysscher, Dirk
中科院分区：
文献类型：
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作者：
Peters, Solange;Felip, Enriqueta;De Ruysscher, Dirk
NICOLAS研究是第一个在III期NSCLC中完成的单组II期试验，首先分级评估在标准确定的同步放化疗中同时添加nivolumab的安全性，然后分级评估有效性。安全终点报告较早；在此，我们提出了疗效结果。方法：IIIA-B期不可切除的非小细胞肺癌患者接受三个周期的铂基化疗和同步放疗（66 Gy， 33个分数），以及纳武单抗（360 mg， 3周）。纳武单抗作为单药巩固治疗持续最多1年（480mg， 4周）。主要终点是1年无进展生存期（PFS），与历史数据相比，目标改善至少15%，从45%提高到60%。为了检验这一功效假设，74名可评估患者的样本量为83%，单侧α为5%。结果：共有79例患者入组，中位随访时间为21.0个月（四分位间距：15.8-25.8个月），用于初步PFS分析。IIIA期占35.4%，IIIB期占63.3%。1年PFS为53.7%(95%可信区间[CI]: 42.0%-64.0%)，中位PFS为12.7个月（95% CI: 10.1-22.8个月）。因为在74名可评估的患者中，37例PFS事件发生在治疗后的第一年，因此1年PFS率至少为45%不能被拒绝（p = 0.23）。在延长随访（中位32.6个月）中，记录了37例死亡，中位总生存期（OS）为38.8个月（95% CI: 26.8个月-无法估计），2年OS率为63.7% （95% CI: 51.9%-73.4%）。IIIA期患者的OS明显高于IIIB期患者，2年OS分别为81%和56% （p = 0.037）。结论：在涉及相同人群的研究中，PFS和OS在算术上更高。然而，在正式的分级疗效分析的基础上，我们不能拒绝1年PFS率至少为45%。(C) 2020年由爱思唯尔公司代表国际肺癌研究协会出版。
Introduction: The NICOLAS study is the first completed single-arm phase II trial in stage III NSCLC evaluating hierarchically first the safety and then the efficacy of adding nivolumab concurrently to standard definitive concurrent chemoradiotherapy. The safety end point was reported earlier; here, we present the efficacy results.Methods: Stage IIIA-B unresectable treatment-naive patients with NSCLC received three cycles of platinum-based chemotherapy and concurrent radiotherapy (66 Gy, 33 fractions), along with nivolumab (360 mg, 3-weekly). Nivolumab was continued as monotherapy consolidation for a maximum of 1 year (480 mg, 4-weekly). The primary end point was 1-year progression-free survival (PFS), with a target improvement compared with historical data of at least 15%, from 45% to 60%. To test this efficacy hypothesis, a sample size of 74 assessable patients provided a power of 83% with a one-sided alpha of 5%.Results: A total of 79 patients were enrolled with a median follow-up of 21.0 months (interquartile range: 15.8-25.8 mo) for the primary PFS analysis. A total of 35.4% of the patients had stage IIIA, and 63.3% had stage IIIB disease. The 1-year PFS was 53.7% (95% confidence interval [CI]: 42.0%-64.0%) and the median PFS was 12.7 months (95% CI: 10.1-22.8 mo). Because 37 PFS events occurred in the first year posttreatment among the first 74 assessable patients, a 1-year PFS rate of at least 45% could not be rejected (p = 0.23). At an extended follow-up (median 32.6 mo), 37 deaths have been recorded, with a median overall survival (OS) of 38.8 months (95% CI: 26.8 mo-not estimable) and a 2-year OS rate of 63.7% (95% CI: 51.9%-73.4%). The OS of patients with stage IIIA disease was found to be significantly higher than patients with stage IIIB disease, with a 2-year OS of 81% and 56%, respectively (p = 0.037).Conclusions: PFS and OS are arithmetically higher in studies involving the same population. However, on the basis of the formal hierarchical efficacy analysis, we could not reject that the 1-year PFS rate is at least 45%. (C) 2020 Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.