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:	Paz-Ares L; Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Universidad Complutense & CiberOnc, Madrid, Spain. Electronic address: lpazaresr@seom.org., Ciuleanu TE; Institutul Oncologic Prof Dr Ion Chiricuta and UMF Iuliu Hatieganu, Cluj-Napoca, Romania., Cobo M; Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain., Schenker M; SF Nectarie Oncology Center, Craiova, Romania., Zurawski B; Ambulatorium Chemioterapii, Bydgoszcz, Poland., Menezes J; Hospital Nossa Senhora Da Conceição, Porto Alegre, Brazil., Richardet E; Instituto Oncológico De Córdoba, Córdoba, Argentina., Bennouna J; Thoracic Oncology Unit, University Hospital of Nantes and INSERM, CRCINA, Nantes, France., Felip E; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain., Juan-Vidal O; Hospital Universitario La Fe, Valencia, Spain., Alexandru A; Institute of Oncology Prof Dr Alexandru Trestioreanu Bucha, Bucharest, Romania., Sakai H; Saitama Cancer Center, Saitama, Japan., Lingua A; Instituto Medico Rio Cuarto SA, Córdoba, Argentina., Salman P; Fundacion Arturo Lopez Perez, Santiago, Metropolitana, Chile., Souquet PJ; Hôpital Lyon Sud, Lyon, Pierre Bénite, France., De Marchi P; Barretos Cancer Hospital, Barretos, Brazil., Martin C; Instituto Alexander Fleming, Buenos Aires, Argentina., Pérol M; Léon Bérard Cancer Center, Lyon, France., Scherpereel A; Pulmonary and Thoracic Oncology, University of Lille, CHU Lille, INSERM U1189, OncoThAI, Lille, France., Lu S; Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China., John T; Austin Hospital, Heidelberg, VIC, Australia., Carbone DP; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Meadows-Shropshire S; Bristol Myers Squibb, Princeton, NJ, USA., Agrawal S; Bristol Myers Squibb, Princeton, NJ, USA., Oukessou A; Bristol Myers Squibb, Princeton, NJ, USA., Yan J; Bristol Myers Squibb, Princeton, NJ, USA., Reck M; Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, LungClinic, Grosshansdorf, Germany.
Jazyk:	angličtina
Zdroj:	The Lancet. Oncology [Lancet Oncol] 2021 Feb; Vol. 22 (2), pp. 198-211. Date of Electronic Publication: 2021 Jan 18.
DOI:	10.1016/S1470-2045(20)30641-0
Abstrakt:	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. (Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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