Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non-Small-Cell Lung Cancer (NADIM phase II trial)
Mariano Provencio, Roberto Serna-Blasco, Ernest Nadal, Amelia Insa, M Rosario García-Campelo, Joaquín Casal Rubio, Manuel Dómine, Margarita Majem, Delvys Rodríguez-Abreu, Alex Martínez-Martí, Javier De Castro Carpeño, Manuel Cobo, Guillermo López Vivanco, Edel Del Barco, Reyes Bernabé Caro, Nuria Viñolas, Isidoro Barneto Aranda, Santiago Viteri, Eva Pereira, Ana Royuela, Virginia Calvo, Javier Martín-López, Francisco García-García, Marta Casarrubios, Fernando Franco, Estela Sánchez-Herrero, Bartomeu Massuti, Alberto Cruz-Bermúdez, Atocha Romero, Mariano Provencio, Roberto Serna-Blasco, Ernest Nadal, Amelia Insa, M Rosario García-Campelo, Joaquín Casal Rubio, Manuel Dómine, Margarita Majem, Delvys Rodríguez-Abreu, Alex Martínez-Martí, Javier De Castro Carpeño, Manuel Cobo, Guillermo López Vivanco, Edel Del Barco, Reyes Bernabé Caro, Nuria Viñolas, Isidoro Barneto Aranda, Santiago Viteri, Eva Pereira, Ana Royuela, Virginia Calvo, Javier Martín-López, Francisco García-García, Marta Casarrubios, Fernando Franco, Estela Sánchez-Herrero, Bartomeu Massuti, Alberto Cruz-Bermúdez, Atocha Romero
Abstract
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/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 3-year OS. ctDNA levels were significantly associated with OS and outperformed radiologic assessments in the prediction of survival.
Conflict of interest statement
Atocha Romero
Consulting or Advisory Role: Takeda, AstraZeneca Spain
Research Funding: Bristol Myers Squibb Foundation (Inst), Boehringer Ingelheim (Inst), Takeda (Inst)
Expert Testimony: Vivo Diagnostics
No other potential conflicts of interest were reported.
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Source: PubMed