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
PURPOSE
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.
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/m
2 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 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
