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Title: 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.
Austin Authors: Paz-Ares, Luis;Ciuleanu, Tudor-Eliade;Cobo, Manuel;Schenker, Michael;Zurawski, Bogdan;Menezes, Juliana;Richardet, Eduardo;Bennouna, Jaafar;Felip, Enriqueta;Juan-Vidal, Oscar;Alexandru, Aurelia;Sakai, Hiroshi;Lingua, Alejo;Salman, Pamela;Souquet, Pierre-Jean;De Marchi, Pedro;Martin, Claudio;Pérol, Maurice;Scherpereel, Arnaud;Lu, Shun;John, Thomas ;Carbone, David P;Meadows-Shropshire, Stephanie;Agrawal, Shruti;Oukessou, Abderrahim;Yan, Jinchun;Reck, Martin
Affiliation: Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Universidad Complutense & CiberOnc, Madrid, Spain
Institutul Oncologic Prof Dr Ion Chiricuta and UMF Iuliu Hatieganu, Cluj-Napoca, Romania
Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain
SF Nectarie Oncology Center, Craiova, Romania
Ambulatorium Chemioterapii, Bydgoszcz, Poland
Hospital Nossa Senhora Da Conceição, Porto Alegre, Brazil
Instituto Oncológico De Córdoba, Córdoba, Argentina
Thoracic Oncology Unit, University Hospital of Nantes and INSERM, CRCINA, Nantes, France
Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain
Hospital Universitario La Fe, Valencia, Spain
Institute of Oncology Prof Dr Alexandru Trestioreanu Bucha, Bucharest, Romania
Saitama Cancer Center, Saitama, Japan
Instituto Medico Rio Cuarto SA, Córdoba, Argentina
Fundacion Arturo Lopez Perez, Santiago, Metropolitana, Chile
Hôpital Lyon Sud, Lyon, Pierre Bénite, France
Barretos Cancer Hospital, Barretos, Brazil
Instituto Alexander Fleming, Buenos Aires, Argentina
Léon Bérard Cancer Center, Lyon, France
Pulmonary and Thoracic Oncology, University of Lille, CHU Lille, INSERM U1189, OncoThAI, Lille, France
Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China
Austin Health
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
Bristol Myers Squibb, Princeton, NJ, USA
Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, LungClinic, Grosshansdorf, Germany
Issue Date: Feb-2021
Date: 2021-01-18
Publication information: The Lancet. Oncology 2021; 22(2): 198-211
Abstract: 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. 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, number NCT03215706. 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. 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. Bristol Myers Squibb.
DOI: 10.1016/S1470-2045(20)30641-0
Journal: The Lancet. Oncology
PubMed URL: 33476593
Type: Journal Article
Subjects: lung cancer treatment
Appears in Collections:Journal articles

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