Titre :

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

Auteur(s) :

Paz-Ares, Luis [Auteur]
Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] [UCM]
Ciuleanu, Tudor-Eliade [Auteur]
Cobo, Manuel [Auteur]
Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina = Biomedical Research Institute of Málaga and Nanomedicine Platform [IBIMA Plataforma BIONAND ]
Schenker, Michael [Auteur]
Zurawski, Bogdan [Auteur]
Menezes, Juliana [Auteur]
Richardet, Eduardo [Auteur]
Bennouna, Jaafar [Auteur]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Immunogenic Cell Death and Mesothelioma Therapy [CRCINA-ÉQUIPE 4]
Felip, Enriqueta [Auteur]
Vall d'Hebron Institute of Oncology [Barcelone] [VHIO]
Juan-Vidal, Oscar [Auteur]
Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe
Alexandru, Aurelia [Auteur]
Sakai, Hiroshi [Auteur]
Lingua, Alejo [Auteur]
Salman, Pamela [Auteur]
Souquet, Pierre-Jean [Auteur]
Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS]
de Marchi, Pedro [Auteur]
Martin, Claudio [Auteur]
Perol, Maurice [Auteur]
Centre Léon Bérard [Lyon]
Scherpereel, Arnaud [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Université de Lille
Thérapies Assistées par Lasers et Immunothérapies pour l'Oncologie - U 1189 [OncoThAI]
Lu, Shun [Auteur]
Shanghai Jiao Tong University [Shanghai]
Thomas, John [Auteur]
Austin Hospital [Melbourne]
Carbone, David [Auteur]
The Ohio State University [Columbus] [OSU]
Meadows-Shropshire, Stéphanie [Auteur]
Bristol-Myers Squibb [Princeton]
Agrawal, Shruti [Auteur]
Bristol-Myers Squibb [Princeton]
Oukessou, Abderrahim [Auteur]
Bristol-Myers Squibb [Princeton]
Yan, Jinchun [Auteur]
Bristol-Myers Squibb [Princeton]
Reck, Martin [Auteur]
German Center for Lung Research

Titre de la revue :

The Lancet

Pagination :

198-211

Éditeur :

Elsevier

Date de publication :

2021

ISSN :

0140-6736

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Cancer

Résumé en anglais : [en]

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) ...
Lire la suite >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.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Commentaire :

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.

Collections :

• Thérapies Lasers Assistées par l'Image pour l'Oncologie (ONCO-THAI) - U1189

Source :

Harvested from HAL