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

Author(s): Mariano Provencio, MD, PhD1;Roberto Serna-Blasco, MSc1;Ernest Nadal, MD2;Amelia Insa, MD3;M. Rosario García-Campelo, MD4;Joaquín Casal Rubio, MD5;Manuel Dómine, MD6;Margarita Majem, MD7;Delvys Rodríguez-Abreu, MD8;Alex Martínez-Martí, MD9;Javier De Castro Carpeño, MD10;Manuel Cobo, MD11;Guillermo López Vivanco, MD12;Edel Del Barco, MD13;Reyes Bernabé Caro, MD14;Nuria Viñolas, MD15;Isidoro Barneto Aranda, MD16;Santiago Viteri, MD17;Eva Pereira, MSc18;Ana Royuela, PhD1;Virginia Calvo, MD1;Javier Martín-López, MD1;Francisco García-García, PhD19;Marta Casarrubios, MSc1;Fernando Franco, MD1;Estela Sánchez-Herrero, MSc1,20;Bartomeu Massuti, MD21;Alberto Cruz-Bermúdez, PhD1;and Atocha Romero, PhD1
Source: DOI: 10.1200/JCO.21.02660
Lucio Gordan MD

Another study showing that ctDNA will absolutely change how we manage and follow patients in a myriad of neoplasms, with decreased utilization of CT scans in the next decade.


Neoadjuvant chemotherapy plus nivolumab has been shown to be effective in resectable non–small-cell 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.


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.


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).


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.

Author Affiliations

1Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain;2Institut Català d’Oncologia, L’Hospitalet De Llobregat, Barcelona, Spain;3Fundación INCLIVA, Hospital Clínico Universitario de Valencia, Valencia, Spain;4Hospital Universitario A Coruña, A Coruña, Spain;5Hospital Universitario de Vigo, Pontevedra, Spain;6Hospital Universitario Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain;7Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;8Hospital Insular de Gran Canaria, Las Palmas, Spain;9Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Barcelona, Spain;10Hospital Universitario La Paz, Madrid, Spain;11Hospital Universitario Regional de Malaga, Spain;12Hospital Universitario Cruces, Barakaldo, Spain.;13Hospital Universitario de Salamanca, Salamanca, Spain;14Hospital Universitario Virgen del Rocio, Seville, Spain;15Hospital Clínic, Barcelona, Spain;16Hospital Universitario Reina Sofia, Córdoba, Spain;17Instituto Oncológico Dr Rosell. Hospital Universitario Quiron Dexeus, Grupo QuironSalud, Barcelona, Spain;18Spanish Lung Cancer Group, Barcelona, Spain;19Centro de Investigación Principe Felipe, Valencia, Spain;20Atrys Health, Barcelona, Spain;21Hospital General de Alicante, Alicante, Spain

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Perioperative Nivolumab in Resectable Lung Cancer

Perioperative nivolumab (Nivo) showed a 20% 18-month EFPS improvement. This is another option to consider for your patients with stage IIA-IIIB NSCLC. Of note, the study arm received chemo + Nivo x 4 cycles preoperatively, then 12 months of Nivo therapy, and toxicities were as expected.

Read More »

Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer

FCS medical oncologist and hematologist Ernesto Bustinza-Linares, MD has co-authored an abstract published in the American Society of Clinical Oncology Journal, JCO Precision Oncology, that uncovers a new testing method to determine personalized care options for patients with metastatic non-small cell lung cancer (NSCLC). The abstract’s authors address the limitations of existing guidelines that recommend checkpoint immunotherapy, sometimes in combination with chemotherapy, for treating NSCLC, which often discounts patient variability and immune factors. The findings from the study show that by incorporating additional plasma proteome-based testing, combined with the standard protein inhibitor testing, clear differences in patient outcomes were observed after applying targeted treatments based on the testing results.

Read More »

Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)

Adding VEGF inhibitor to PD-1 blocker in addition to chemotherapy is better than a chemotherapy-alone regimen as a second-line therapy after TKI failure. This is true especially in patients with tumors with high PD-L1 expression, with not much besides chemotherapy as second-line therapy for those patients (or other clinical trials) that may be a better option that includes immunotherapy.

Read More »

Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor–Mutated Metastatic Non–Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722

This is the same issue as the Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04) article, this one was negative though. A question for the previous trial would be: do we need PDL-1 inhibitor, or just VEGF inhibitor, recall the pts with tumors with high PDL-1 expression did better though, so most likely we need both with chemotherapy.

Read More »