1. Efficacy and safety of first-line checkpoint inhibitors-based treatments for non-oncogene-addicted non-small-cell lung cancer: a systematic review and meta-analysis
- Author
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Siciliano, M A, Caridà, G, Ciliberto, D, d'Apolito, M, Pelaia, C, Caracciolo, D, Riillo, C, Correale, P, Galvano, A, Russo, A, Barbieri, V, Tassone, P, Tagliaferri, P, Siciliano, M A, Caridà, G, Ciliberto, D, d'Apolito, M, Pelaia, C, Caracciolo, D, Riillo, C, Correale, P, Galvano, A, Russo, A, Barbieri, V, Tassone, P, and Tagliaferri, P
- Subjects
Cancer Research ,Lung Neoplasms ,checkpoints inhibitors ,Ipilimumab ,B7-H1 Antigen ,Bevacizumab ,Antineoplastic Agents, Immunological ,Nivolumab ,non-small-cell lung cancer ,systematic review ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Humans ,network meta-analysis ,frontline therapy - Abstract
Background: Frontline immune checkpoint inhibitors (ICI)-based regimens in non-oncogene-addicted non-small-cell lung cancer (NSCLC) have been deeply investigated. To rank the available therapeutic options, we carried out a systematic review and Bayesian meta-analysis. Methods: A comprehensive search for randomized controlled trials (RCTs) of ICI regimens, and a pairwise and a network meta-analysis (NMA) with an all-comers and a stratified strategy were conducted. Endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (TRAEs). Results: Nineteen RCTs involving 17 treatment regimens were included. For the all-comers population, pembrolizumab/ chemotherapy (CT) and cemiplimab were most likely the best treatments. For programmed death-ligand 1 (PD-L1) < 1% nivolumab/ipilimumab with/without CT, for PD-L1 > 1% and 1%-49% pembrolizumab/CT and for PD-L1 > 50% cemiplimab ranked first for OS. In non-squamous (NSQ), pembrolizumab with/without CT ranked first for OS; cemiplimab ranked worse than the unselected population. In squamous (SQ), pooled hazard ratio (HR) showed a better chance in improving efficacy for combination strategy, while monotherapy did not, except for cemiplimab that ranked second. Atezolizumab/CT/bevacizumab ranked first in most subgroups for PFS. Direct comparison showed a non-statistically significant benefit of ICI regimens for the liver metastases cohort in OS, with a good ranking for pembrolizumab/CT and atezolizumab/bevacizumab/CT. Regarding brain metastases, all ICI regimens demonstrated an improvement in OS and PFS compared to CT. Nivolumab/ipilimumab/CT ranked better in this subset. Conclusions: Our meta-analysis updated on the most recent findings demonstrates that different ICI treatments rank differently in specific NSCLC settings (histology, biomarker and clinical presentation) offering a novel challenging scenario for clinical decision making and research planning.
- Published
- 2022