单抗联合化疗治疗可手术的NSCLC的总生存期和生物标志物分析

SCI

18 June 2022

Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non–Small-Cell Lung Cancer (NADIM phase II trial)

( IF: JCO, 44.544)

• Provencio M, Serna-Blasco R, Nadal E, Insa A, García-Campelo MR, Casal Rubio J, Dómine M, Majem M, Rodríguez-Abreu D, Martínez-Martí A, De Castro Carpeño J, Cobo M, López Vivanco G, Del Barco E, Bernabé Caro R, Viñolas N, Barneto Aranda I, Viteri S, Pereira E, Royuela A, Calvo V, Martín-López J, García-García F, Casarrubios M, Franco F, Sánchez-Herrero E, Massuti B, Cruz-Bermúdez A, Romero A. Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non-Small-Cell Lung Cancer (NADIM phase II trial). J Clin Oncol. 2022 May 16:JCO2102660. 

• CORRESPONDING AUTHORMariano Provencio, MD, PhD, Medical Oncology Department, Hospital，Puerta de Hierro, Calle Joaqu´ın Rodrigo, 1, 28222 Majadahonda, Madrid,Spain; Twitter: @MARIANOPROVENCI; e-mail: mprovenciop@gmail.com.

PURPOSE 目的

Neoadjuvant chemotherapy plus nivolumab has been shown to be effective in resectable non–smallcell lung cancer (NSCLC) in the NADIM trial (ClinicalTrials.gov identifier: NCT03081689). The 3-year overall survival (OS) and circulating tumor DNA (ctDNA) analysis have not been reported.

NADIM试验（ClinicalTrials.gov标识符：NCT03081689）表明，新辅助化疗联合纳武利尤单抗对可切除的非小细胞肺癌（NSCLC）有效。尚未有3年总生存期（OS）和循环肿瘤DNA（cDNA）分析的报道。

METHODS 方法

This was an open-label, multicenter, single-arm, phase II trial in which patients with stage IIIA NSCLC, who were deemed to be surgically resectable, were treated with neoadjuvant paclitaxel (200 mg/m2 once a day) and carboplatin (area under curve 6) plus nivolumab (360 mg) once on day 1 of each 21-day cycle, for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The 3-year OS and ctDNA analysis were secondary objectives of the trial.

这是一项开放标签、多中心、单臂、II期试验，其中，被认为可以手术切除的IIIA期非小细胞肺癌患者，在每21天周期的第1天接受新辅助紫杉醇（200 mg/m2，每天一次）和卡铂（曲线6下的面积）加纳武利尤单抗（360 mg）治疗，共三个周期，然后辅助纳武利尤单抗单药治疗1年（240毫克，每2周一次，持续4个月，然后480毫克，每4周一次，持续8个月）。3年的OS和ctDNA分析是该试验的次要目标。

RESULTS 结果

OS at 36 months was 81.9% (95% CI, 66.8 to 90.6) in the intention-to-treat population, rising to 91.0% (95% CI, 74.2 to 97.0) in the per-protocol population. Neither tumor mutation burden nor programmed cell death ligand-1 staining was predictive of survival. Conversely, low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and OS (hazard ratio [HR]: 0.20; 95% CI, 0.06 to 0.63, and HR: 0.07; 95% CI, 0.01 to 0.39, respectively). Clinical responses according to RECIST v1.1 criteria did not predict survival outcomes. However, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and OS (HR: 0.26; 95% CI, 0.07 to 0.93, and HR: 0.04; 95% CI, 0.00 to 0.55, respectively). The C-index to predict OS for ctDNA levels after neoadjuvant treatment (0.82) was superior to that of RECIST criteria (0.72).

在意向治疗人群中，36个月时的OS为81.9%（95% CI，66.8-90.6），在符合方案人群中上升到了91.0%（95% CI，74.2-97.0）。肿瘤突变负荷和程序性细胞死亡配体-1染色均不能预测生存率。相反，治疗前低水平的ctDNA与无进展生存期和OS的改善显著相关（风险比【HR】:0.20；95% CI，0.06至0.63, 以及HR:0.07；95% CI，0.01至0.39）。根据RECIST v1.1标准的临床反应不能预测生存结果。然而，新辅助治疗后检测不到的ctDNA水平与无进展生存期和OS显著相关（HR:0.26；95% CI, 0.07至0.93，HR:0.04；95% CI, 0.00至0.55）。新辅助治疗后ctDNA水平预测OS的C指数(0.82)优于RECIST标准(0.72)。

CONCLUSION 结论

The efficacy of neoadjuvant chemotherapy plus nivolumab in resectable NSCLC is supported by 3- year OS. ctDNA levels were significantly associated with OS and outperformed radiologic assessments in the prediction of survival.

新辅助化疗联合纳武利尤单抗治疗可切除非小细胞肺癌的疗效得到3年OS的支持。ctDNA水平与OS显著相关，在预测生存率方面优于放射学评估。

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