1. Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial.
- Author
-
Provencio M, Nadal E, Insa A, García Campelo R, Casal J, Dómine M, Massuti B, Majem M, Rodríguez-Abreu D, Martínez-Martí A, de Castro J, Gómez de Antonio D, Macia I, Figueroa S, Fernández Vago L, Calvo V, Palmero R, Sierra-Rodero B, Martínez-Toledo C, Molina-Alejandre M, Serna-Blasco R, Romero A, and Cruz-Bermúdez A
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Progression-Free Survival, Chemotherapy, Adjuvant, Spain, Paclitaxel administration & dosage, Paclitaxel adverse effects, Carboplatin administration & dosage, Nivolumab administration & dosage, Nivolumab adverse effects, Nivolumab therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung mortality, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Lung Neoplasms mortality, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Neoadjuvant Therapy adverse effects
- Abstract
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/m
2 ) 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., Funding: Bristol-Myers Squibb, Spanish Ministry of Science, Instituto de Salud Carlos III, European Union., Competing Interests: Declaration of interests MP reports non-financial support (reagents for T-cell receptor sequencing) from ThermoFisher Scientific; grants, consulting fees, and non-financial support from Bristol Myers Squibb, Roche, and AstraZeneca; and consulting fees from MSD and Takeda; outside the submitted work. EN reports grants from Roche, Pfizer, Bristol Myers Squibb, Merck, and Nanostring; consulting fees from Roche, Bristol Myers Squibb, Merck Sharpe & Dohme, Merck-Serono, Sanofi, Pfizer, Lilly, Amgen, Janssen, Daiichi-Sankyo, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, Qiagen, and Bayer; payment of honoraria from Roche, Bristol Myers Squibb, Merck Sharpe & Dohme, Sanofi, Pfizer, Lilly, Amgen, Janssen, Daiichi-Sankyo, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, and Qiagen; support for attending meetings or travel from Takeda, MSD, Janssen, and Roche; and participation on advisory boards for Apollomics, Roche, and Pfizer. AI reports consulting fees from Pfizer, Amgen, and Astra Zeneca; payment for expert testimony from Bristol Myers Squibb, Roche, Pfizer, Astra Zeneca, and Takeda; support for attending meetings or travel from Roche, Takeda, and Pfizer; and participation on advisory boards for Roche and Bristol Myers Squibb. RG-C reports consulting fees from Bristol Myers Squibb, MSD, Roche, Pfizer, and AstraZeneca. MD reports consulting fees from AstraZeneca, Bristol Myers Squibb, MSD Oncology, Pfizer, Roche, and Takeda; and support for attending meetings or travel from AstraZeneca, MSD Oncology, Pfizer, and Takeda. BM reports consulting fees from Astra Zeneca and Amgen; payment or honoraria from Roche, Bristol Myers Squibb, and MSD; and support for attending meetings or travel from MSD and AstraZeneca. MM reports grants from Roche and Astra Zeneca; payment of honoraria from Roche, AstraZeneca, MSD, Pfizer, Helsinn, Cassen, Amgen, Janssen, Sanofi, Pierre Fabre, Bristol Myers Squibb, and Takeda; and support for attending meetings or travel from MSD, Roche, and AstraZeneca. DR-A reports honoraria for lectures from MSD, Roche, Bristol Myers Squibb, Novartis, Takeda, Lilly, and AstaZeneca; support for attending meetings or travel from Roche, MSD, Novartis, and Sanofi; and participation on advisory boards for Merck Sharpe & Dohme, Regeneron, Bristol Myers Squibb, GSK, and Lilly. AM-M reports consulting fees from AstraZeneca/MedImmune, Bristol Myers Squibb, F. Hoffmann La Roche, Merck Sharpe & Dohme, MSD Oncology, Pfizer, and Janssen; payment for expert testimony from AstraZeneca, MedImmune, Bristol Myers Squibb, and F. Hoffmann La Roche; support for attending meetings or travel from AstraZeneca, MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche, Merck Sharpe & Dohme, MSD Oncology, Pfizer, Janssen, and Lilly; and participation on advisory boards for AstraZeneca, MedImmune, Merck Sharpe & Dohme, F. Hoffmann La Roche, and Bristol-Myers Squibb. JdC reports consulting fees from AstraZeneca, Bristol Myers Squibb, Roche, MSD, Boehringer, Janssen, Lilly, Sanofi, Takeda, Pfizer, and GSK; support for attending meeting or travel from AstraZeneca, MSD, and Roche; participation on advisory boards for AstraZeneca, Bristol Myers Squibb, Roche, MSD, Glaxo, Janssen, and Gilea; and speaker's bureau fees from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche, Merck Sharpe & Dohme, MSD Oncology, Pfizer, and Janssen. DG reports payment or honoraria from Astra Zeneca and Bristol Myers Squibb. VC reports consulting fees from Roche, AstraZeneca, MSD, Bristol Myers Squibb, Takeda, Sanofi, and Amgen; payment or honoraria from Roche, AstraZeneca, MSD, Bristol Myers Squibb, Takeda, SanofiI, and Amgen; and support for attending meetings or travel from AstraZeneca, Roche, MSD, and Takeda. RP reports payment or honoraria from Guardant Health and Pfizer; and support for attending meetings or travel from Merck Sharpe & Dohme; participation on an advisory board for AstraZeneca. AR reports payment or honoraria from Illumina, Health in Code, and ThermoFisher Scientific; support for attending meetings or travel from ThermoFisher Scientific, Bristol Myers Squibb Foundation, and Takeda; and advisory board participation for Takeda. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF