First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial

Autor: Pierre-Jean Souquet, David P. Carbone, Michael Schenker, Shun Lu, S. Meadows-Shropshire, A. Alexandru, Pamela Salman, Hiroshi Sakai, Jaafar Bennouna, Maurice Pérol, Enriqueta Felip, Alejo Lingua, J. Yan, Juliana Janoski de Menezes, B. Zurawski, Martin Reck, Arnaud Scherpereel, C. Martin, Eduardo Richardet, Abderrahim Oukessou, Tudor-Eliade Ciuleanu, Manuel Cobo, O. Juan-Vidal, Pedro Rafael Martins De Marchi, Thomas John, Luis Paz-Ares, Shruti Agrawal
Přispěvatelé: Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), The Oncology Institute 'Prof. Dr. Ion Chiricuţă' [Cluj-Napoca, Romania] (TOI), Instituto de Investigación Biomédica [Malaga, Spain] (IBIMA), SF Nectarie Oncology Center [Craiova, Romania], Ambulatorium Chemioterapii [Bydgoszcz, Poland] (AC), Hospital Nossa Senhora Da Conceição [Porto Alegre, Brazil] (HNSDC), Instituto Oncológico De Córdoba [Córdoba, Argentina] (IODC), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre hospitalier universitaire de Nantes (CHU Nantes), Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Hospital Universitario La Fe [Valencia, Spain] (HU), Oncology Institute of Bucharest Professor Doctor Alexandru Trestioreanu [Bucharest, Romania] (OIB), Saitama Cancer Center [Saitama, Japan] (S2C), Instituto Medico Rio Cuarto SA [Córdoba, Argentina] (IMRC), Fundacion Arturo Lopez Perez [Santiago, Metropolitana, Chile] (FALP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Barretos Cancer Hospital [São Paulo, Brazil], Instituto Alexander Fleming [Buenos Aires, Argentina] (IAF), Centre Léon Bérard [Lyon], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Lille, CHU Lille, Shanghai Jiao Tong University [Shanghai], Austin Hospital [Melbourne], Austin Health, Ohio State University [Columbus] (OSU), Bristol-Myers Squibb [Princeton], German Center for Lung Research, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Bernardo, Elizabeth
Rok vydání: 2021
Předmět:
Zdroj: LANCET ONCOLOGY
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
instname
Lancet
Lancet, Elsevier, 2021, 22 (2), pp.198-211. ⟨10.1016/S1470-2045(20)30641-0⟩
The Lancet
The Lancet, 2021, 22 (2), pp.198-211. ⟨10.1016/S1470-2045(20)30641-0⟩
ISSN: 1470-2045
0140-6736
1474-547X
Popis: Erratum in Correction to Lancet Oncol 2021; 22: 198-211. [No authors listed] Lancet Oncol. 2021 Mar;22(3):e92. doi: 10.1016/S1470-2045(21)00082-6. PMID: 33662299 No abstract available.; International audience; Background: First-line nivolumab plus ipilimumab has shown improved overall survival in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to investigate whether the addition of a limited course (two cycles) of chemotherapy to this combination would further enhance the clinical benefit.Methods: This randomised, open-label, phase 3 trial was done at 103 hospitals in 19 countries. Eligible patients were aged 18 years or older with treatment-naive, histologically confirmed stage IV or recurrent NSCLC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients were randomly assigned (1:1) by an interactive web response system via permuted blocks (block size of four) to nivolumab (360 mg intravenously every 3 weeks) plus ipilimumab (1 mg/kg intravenously every 6 weeks) combined with histology-based, platinum doublet chemotherapy (intravenously every 3 weeks for two cycles; experimental group), or chemotherapy alone (every 3 weeks for four cycles; control group). Randomisation was stratified by tumour histology, sex, and PD-L1 expression. The primary endpoint was overall survival in all randomly assigned patients. Safety was analysed in all treated patients. Results reported here are from a pre-planned interim analysis (when the study met its primary endpoint) and an exploratory longer-term follow-up analysis. This study is active but no longer recruiting patients, and is registered with ClinicalTrials.gov, number NCT03215706.Findings: Between Aug 24, 2017, and Jan 30, 2019, 1150 patients were enrolled and 719 (62·5%) randomly assigned to nivolumab plus ipilimumab with two cycles of chemotherapy (n=361 [50%]) or four cycles of chemotherapy alone (n=358 [50%]). At the pre-planned interim analysis (median follow-up 9·7 months [IQR 6·4-12·8]), overall survival in all randomly assigned patients was significantly longer in the experimental group than in the control group (median 14·1 months [95% CI 13·2-16·2] vs 10·7 months [9·5-12·4]; hazard ratio [HR] 0·69 [96·71% CI 0·55-0·87]; p=0·00065). With 3·5 months longer median follow-up (median 13·2 months [IQR 6·4-17·0]), median overall survival was 15·6 months (95% CI 13·9-20·0) in the experimental group versus 10·9 months (9·5-12·6) in the control group (HR 0·66 [95% CI 0·55-0·80]). The most common grade 3-4 treatment-related adverse events were neutropenia (in 24 [7%] patients in the experimental group vs 32 [9%] in the control group), anaemia (21 [6%] vs 50 [14%]), diarrhoea (14 [4%] vs two [1%]), increased lipase (22 [6%] vs three [1%]), and asthenia (tjree [1%] vs eight [2%]). Serious treatment-related adverse events of any grade occurred in 106 (30%) patients in the experimental group and 62 (18%) in the control group. Seven (2%) deaths in the experimental group (acute kidney failure, diarrhoea, hepatotoxicity, hepatitis, pneumonitis, sepsis with acute renal insufficiency, and thrombocytopenia; one patient each) and six (2%) deaths in the control group (anaemia, febrile neutropenia, pancytopenia, pulmonary sepsis, respiratory failure, and sepsis; one patient each) were treatment related.Interpretation: Nivolumab plus ipilimumab with two cycles of chemotherapy provided a significant improvement in overall survival versus chemotherapy alone and had a favourable risk-benefit profile. These data support this regimen as a new first-line treatment option for patients with advanced NSCLC.Funding: Bristol Myers Squibb.
Databáze: OpenAIRE
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