Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis.

Détails

ID Serval
serval:BIB_C3ECA1D23C4B
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis.
Périodique
Lung cancer
Auteur(s)
Dafni U., Tsourti Z., Vervita K., Peters S.
ISSN
1872-8332 (Electronic)
ISSN-L
0169-5002
Statut éditorial
Publié
Date de publication
08/2019
Peer-reviewed
Oui
Volume
134
Pages
127-140
Langue
anglais
Notes
Publication types: Journal Article ; Meta-Analysis ; Systematic Review
Publication Status: ppublish
Résumé
This network meta-analysis (NMA), based on 12 phase-III studies with 9,236 metastatic NSCLC patients, aims to compare the efficacy of treatments including at least one immune-checkpoint inhibitor (ICI) with or without chemotherapy, as frontline therapy for advanced NSCLC patients. The NMA includes direct randomized evidence on treatments of interest along with indirect evidence from randomized studies with chemotherapy as the common comparator. Studies were identified by searching PubMed, and the abstracts of most recent main oncology congresses. The primary endpoint, Hazard-Ratio (HR) of Progression-free Survival (PFS), was estimated by a frequentist-approach NMA. Results are presented in the overall cohort (all-comers or PD-L1-positive) irrespective of histology, and by histology, PD-L1 expression level and sex. According to the primary PFS-NMA in the overall cohort, the combination of chemotherapy, first with pembrolizumab, second with atezolizumab exhibit significantly higher benefit than any other treatment examined. This superior PFS benefit is found for both squamous and non-squamous patients. Similarly for OS, the combination of pembrolizumab/chemotherapy, and atezolizumab/bevacizumab/chemotherapy-(ABC), followed by pembrolizumab-monotherapy and atezolizumab/chemotherapy, are the best treatments in the overall cohort, driven by the non-squamous histology. In the PD-L1-high patients again the combination of chemotherapy with atezolizumab or pembrolizumab, exhibit significant PFS benefit, followed by pembrolizumab-monotherapy. PFS benefit of these ICI/chemotherapy combinations are also found in PD-L1-negative and PD-L1-intermediate patients(1%≤PD-L1 < 50%). Of note, ABC is evaluated only for OS in non-squamous patients while the pembrolizumab-monotherapy PFS benefit and the atezolizumab/chemotherapy OS benefit are probably under-estimated since most of the data stems from non-significant interim analyses of ongoing studies [KN042;IM131/132/150]. In conclusion, the addition of chemotherapy to ICIs enhanced their treatment efficacy as first-line treatment for advanced NSCLC patients. The combination of chemotherapy with either pembrolizumab or atezolizumab show consistently higher efficacy than chemotherapy-alone or any other ICI-combination or monotherapy, particularly in non-squamous patients.
Mots-clé
Antineoplastic Agents, Immunological/administration & dosage, Antineoplastic Agents, Immunological/adverse effects, Antineoplastic Agents, Immunological/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, B7-H1 Antigen/genetics, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/etiology, Carcinoma, Non-Small-Cell Lung/mortality, Carcinoma, Non-Small-Cell Lung/pathology, Female, Gene Expression, Humans, Liver Neoplasms/secondary, Lung Neoplasms/drug therapy, Lung Neoplasms/etiology, Lung Neoplasms/mortality, Lung Neoplasms/pathology, Male, Molecular Targeted Therapy, Mutation, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Advanced non-small cell lung cancer, First-line, ICI, Immunotherapy, Network meta-analysis, PD-L1 expression
Pubmed
Web of science
Création de la notice
04/08/2019 16:18
Dernière modification de la notice
07/07/2020 6:20
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