Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non-Small-Cell Lung Cancer (NADIM phase II trial)
Por:
Provencio M., Serna-Blasco R., Nadal E., Insa A., García-Campelo M.R., 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.
Publicada:
1 ene 2022
Resumen:
PURPOSENeoadjuvant 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.METHODSThis 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.RESULTSOS 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).CONCLUSIONThe 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. © American Society of Clinical Oncology.
Filiaciones:
Provencio M.:
Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
Serna-Blasco R.:
Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
Nadal E.:
Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain
Insa A.:
Fundación INCLIVA, Hospital Clínico, Universitario de Valencia, Valencia, Spain
García-Campelo M.R.:
Hospital Universitario A Coruña, A Coruña, Spain
Casal Rubio J.:
Hospital Universitario de Vigo, Pontevedra, Spain
Dómine M.:
Hospital Universitario Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain
Majem M.:
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Rodríguez-Abreu D.:
Hospital Insular de Gran Canaria, Las Palmas, Spain
Martínez-Martí A.:
Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Barcelona, Spain
De Castro Carpeño J.:
Hospital Universitario La Paz, Madrid, Spain
Cobo M.:
Hospital Universitario Regional de Malaga, Spain
López Vivanco G.:
Hospital Universitario Cruces, Barakaldo, Spain
Del Barco E.:
Hospital Universitario de Salamanca, Salamanca, Spain
Bernabé Caro R.:
Hospital Universitario Virgen Del Rocio, Seville, Spain
Viñolas N.:
Hospital Clínic, Barcelona, Spain
Barneto Aranda I.:
Hospital Universitario Reina Sofía, Córdoba, Spain
Viteri S.:
Instituto Oncológico Dr. Rosell, Hospital Universitario Quiron Dexeus, Grupo QuironSalud, Barcelona, Spain
Pereira E.:
Spanish Lung Cancer Group, Barcelona, Spain
Royuela A.:
Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
Calvo V.:
Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
Martín-López J.:
Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
García-García F.:
Centro de Investigación Príncipe Felipe, Valencia, Spain
Casarrubios M.:
Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
Franco F.:
Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
Sánchez-Herrero E.:
Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
Atrys Health, Barcelona, Spain
Massuti B.:
Hospital General de Alicante, Alicante, Spain
Cruz-Bermúdez A.:
Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
Romero A.:
Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
|