Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer: The Lung-MAP S1400I Phase 3 Randomized Clinical Trial.
JAMA Oncol
; 7(9): 1368-1377, 2021 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-34264316
ABSTRACT
IMPORTANCE Nivolumab plus ipilimumab is superior to platinum-based chemotherapy in treatment-naive advanced non-small cell lung cancer (NSCLC). Nivolumab is superior to docetaxel in advanced pretreated NSCLC. OBJECTIVE:
To determine whether the addition of ipilimumab to nivolumab improves survival in patients with advanced, pretreated, immunotherapy-naive squamous (Sq) NSCLC. DESIGN, SETTING, ANDPARTICIPANTS:
The Lung Cancer Master Protocol (Lung-MAP) S1400I phase 3, open-label randomized clinical trial was conducted from December 18, 2015, to April 23, 2018, randomizing patients in a 11 ratio to nivolumab alone or combined with ipilimumab. The median follow-up in surviving patients was 29.5 months. The trial was conducted through the National Clinical Trials Network and included patients with advanced immunotherapy-naive SqNSCLC and a Zubrod score of 0 (asymptomatic) to 1 (symptomatic but completely ambulatory) with disease progression after standard platinum-based chemotherapy. Randomization was stratified by sex and number of prior therapies (1 vs 2 or more). Data were analyzed from May 3, 2018, to February 1, 2021.INTERVENTIONS:
Nivolumab, 3 mg/kg intravenously every 2 weeks, with or without ipilimumab, 1 mg/kg intravenously every 6 weeks, until disease progression or intolerable toxic effects. MAIN OUTCOMES ANDMEASURES:
The primary end point was overall survival (OS). Secondary end points included investigator-assessed progression-free survival (IA-PFS) and response per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1.RESULTS:
Of 275 enrolled patients, 252 (mean age, 67.5 years [range 41.8-90.3 years]; 169 men [67%]; 206 White patients [82%]) were deemed eligible (125 randomized to nivolumab/ipilimumab and 127 to nivolumab). The study was closed for futility at a planned interim analysis. Overall survival was not significantly different between the groups (hazard ratio [HR], 0.87; 95% CI, 0.66-1.16; P = .34). Median survival was 10 months (95% CI, 8.0-14.4 months) in the nivolumab/ipilimumab group and 11 months (95% CI, 8.6-13.7 months) in the nivolumab group. The IA-PFS HR was 0.80 (95% CI, 0.61-1.03; P = .09); median IA-PFS was 3.8 months (95% CI, 2.7-4.4 months) in the nivolumab/ipilimumab group and 2.9 months (95% CI, 1.8-4.0 months) in the nivolumab alone group. Response rates were 18% (95% CI, 12%-25%) with nivolumab/ipilimumab and 17% (95% CI, 10%-23%) with nivolumab. Median response duration was 28.4 months (95% CI, 4.9 months to not reached) with nivolumab/ipilimumab and 9.7 months with nivolumab (95% CI, 4.2-23.1 months). Grade 3 or higher treatment-related adverse events occurred in 49 of 124 patients (39.5%) who received nivolumab/ipilimumab and in 41 of 123 (33.3%) who received nivolumab alone. Toxic effects led to discontinuation in 31 of 124 patients (25%) on nivolumab/ipilimumab and in 19 of 123 (15%) on nivolumab. CONCLUSIONS AND RELEVANCE In this phase 3 randomized clinical trial, ipilimumab added to nivolumab did not improve outcomes in patients with advanced, pretreated, immune checkpoint inhibitor-naive SqNSCLC. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT02785952.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Escamosas
/
Carcinoma Pulmonar de Células não Pequenas
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Neoplasias Pulmonares
Tipo de estudo:
Clinical_trials
/
Guideline
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
JAMA Oncol
Ano de publicação:
2021
Tipo de documento:
Article