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

被引：242

作者：

Provencio, Mariano ^{[1
]}

Serna-Blasco, Roberto ^{[1
]}

Nadal, Ernest ^{[2
]}

Insa, Amelia ^{[3
]}

Rosario Garcia-Campelo, M. ^{[4
]}

Casal Rubio, Joaquin ^{[5
]}

Domine, Manuel ^{[6
]}

Majem, Margarita ^{[7
]}

Rodriguez-Abreu, Delvys ^{[8
]}

Martinez-Marti, Alex ^{[9
]}

De Castro Carpeno, Javier ^{[10
]}

Cobo, Manuel ^{[11
]}

Lopez Vivanco, Guillermo ^{[12
]}

Del Barco, Edel ^{[13
]}

Bernabe Caro, Reyes ^{[14
]}

Vinolas, Nuria ^{[15
]}

Barneto Aranda, Isidoro ^{[16
]}

Viteri, Santiago ^{[17
]}

Pereira, Eva ^{[18
]}

Royuela, Ana ^{[1
]}

Calvo, Virginia ^{[1
]}

Martin-Lopez, Javier ^{[1
]}

Garcia-Garcia, Francisco ^{[19
]}

Casarrubios, Marta ^{[1
]}

Franco, Fernando ^{[1
]}

Sanchez-Herrero, Estela ^{[1
,20
]}

Massuti, Bartomeu ^{[21
]}

Cruz-Bermudez, Alberto ^{[1
]}

Romero, Atocha ^{[1
]}

机构：

[1] Hosp Univ Puerta de Hierro Majadahonda, Madrid, Spain

[2] Inst Catal a Oncol, Barcelona, Spain

[3] Hosp Clin Univ Valencia, Fdn INCLIVA, Valencia, Spain

[4] Hosp Univ A Coruna, La Coruna, Spain

[5] Hosp Univ Vigo, Pontevedra, Spain

[6] Hosp Univ Fdn Jimenez Diaz IIS FJD, Madrid, Spain

[7] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[8] Hosp Insular Gran Canaria, Las Palmas Gran Canaria, Spain

[9] Hosp Univ Vall dHebron, Vall dHebron Inst Oncol VHIO, Barcelona, Spain

[10] Hosp Univ La Paz, Madrid, Spain

[11] Hosp Univ Reg Malaga, Malaga, Spain

[12] Hosp Univ Cruces, Baracaldo, Spain

[13] Hosp Univ Salamanca, Salamanca, Spain

[14] Hosp Univ Virgen del Rocio, Seville, Spain

[15] Hosp Clin Barcelona, Barcelona, Spain

[16] Hosp Univ Reina Sofia, Cordoba, Spain

[17] Hosp Univ Quiron Dexeus, Grp QuironSalud, Inst Oncol Dr Rosell, Barcelona, Spain

[18] Spanish Lung Canc Grp, Barcelona, Spain

[19] Ctr Invest Principe Felipe, Valencia, Spain

[20] Atrys Hlth, Barcelona, Spain

[21] Hosp Gen Alicante, Alicante, Spain

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2022年 / 40卷 / 25期

基金：

欧盟地平线“2020”;

关键词：

CIRCULATING TUMOR DNA; OPEN-LABEL; MULTICENTER; DOCETAXEL; THERAPY; TIME;

D O I：

10.1200/JCO.21.02660

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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

引用

页码：2924 / +

页数：11

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