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cc-by-nc-nd (c) Provencio, Mariano et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/217418

Perioperative chemotherapy and nivolumab in non-small cell lung cancer (NADIM): 5-year clinical outcomes from a multicenter, single-arm, phase 2 trial

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Background: Perioperative immunotherapy improves short-term outcomes in resectable non-small-cell lung cancer (NSCLC). We now report 5-year survival from the NADIM trial to assess its long-term benefit. Methods: NADIM was a multicentre, single-arm, phase 2 trial conducted across 18 hospitals in Spain. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had histologically or cytologically confirmed, treatment-naive, resectable stage IIIA NSCLC (American Joint Committee on Cancer, 7th edition criteria). The neoadjuvant treatment consisted of three cycles of intravenous paclitaxel (200 mg/m2) and carboplatin (area under the curve 6 mg/mL per min) with nivolumab (360 mg). After surgery, 1 year of adjuvant treatment with intravenous nivolumab monotherapy was administered (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was 24-month progression-free survival, with 5-year progression-free survival and overall survival as secondary endpoints, assessed in the intention-to-treat population (ie, all patients who received neoadjuvant treatment). Toxicity profile was also assessed as a secondary endpoint. This trial is registered at ClinicalTrials.gov (NCT03081689) and is complete; this is the final report of the trial. Findings: Between April 26, 2017, and Aug 25, 2018, 51 patients were assessed for eligibility, of whom 46 comprised the intention-to-treat population (34 [74%] male and 12 [26%] female, median age 63 years [IQR 58-70]). Follow-up was concluded at 60 months (data cutoff July 11, 2023; median follow-up 60·0 months [IQR 60·0-60·0]). 5-year progression-free survival in the intention-to-treat population was 65·0% (95% CI 49·4-76·9), and overall survival was 69·3% (53·7-80·6). Disease progression occurred in 11 (24%) patients; 14 (30%) patients died, including nine (20%) from disease relapse and five (11%) from non-tumour-related causes. Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 14 (30%) of 46 patients during neoadjuvant treatment and in seven (19%) of 37 during adjuvant treatment. The most common grade 3 or worse TRAEs were increased lipase and febrile neutropenia (three [7%] each) during neoadjuvant treatment, and elevated serum lipase (four [7%]) and elevated serum amylase (three [8%]) during adjuvant treatment. Serious TRAEs included elevated serum lipase and neutropenia (one [2%] each) during neoadjuvant treatment, and elevated serum lipase (one [3%]) during adjuvant treatment. No treatment-related surgery delays, deaths, or unexpected long-term toxicities were reported. Interpretation: Perioperative chemoimmunotherapy showed a promising long-term benefit with no concerning safety data, reinforcing its use in resectable stage IIIA NSCLC.

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PROVENCIO, Mariano, NADAL, Ernest, INSA, Amelia, GARCÍA CAMPELO, Rosario, CASAL, Joaquín, DÓMINE, Manuel, MASSUTI, Bartomeu, MAJEM, Margarita, RODRÍGUEZ ABREU, Delvys, MARTÍNEZ-MARTÍ, Alex, CASTRO, Javier de, GÓMEZ DE ANTONIO, David, MACÍA, Ivan, FIGUEROA, Santiago, FERNÁNDEZ VAGO, Luís, CALVO, Virginia, PALMERO, Ramón, SIERRA RODERO, Belén, MARTÍNEZ-TOLEDO, Cristina, MOLINA-ALEJANDRE, Marta, SERNA-BLASCO, Roberto, ROMERO, Atocha, CRUZ-BERMÚDEZ, Alberto. Perioperative chemotherapy and nivolumab in non-small cell lung cancer (NADIM): 5-year clinical outcomes from a multicenter, single-arm, phase 2 trial. _The Lancet Oncology_. 2024. Vol. 25, núm. 11, pàgs. 1453-1464. [consulta: 11 de desembre de 2025]. ISSN: 1470-2045. [Disponible a: https://hdl.handle.net/2445/217418]

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