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

M A Siciliano; G Caridà; D Ciliberto; M d'Apolito; C Pelaia; D Caracciolo; C Riillo; P Correale; A Galvano; A Russo; V Barbieri; P Tassone; P Tagliaferri

doi:10.1016/j.esmoop.2022.100465

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

ESMO Open. 2022 Jun;7(3):100465. doi: 10.1016/j.esmoop.2022.100465. Epub 2022 Apr 12.

Authors

M A Siciliano¹, G Caridà¹, D Ciliberto², M d'Apolito¹, C Pelaia¹, D Caracciolo¹, C Riillo¹, P Correale³, A Galvano⁴, A Russo⁴, V Barbieri⁵, P Tassone¹, P Tagliaferri⁶

Affiliations

¹ Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
² Mater Domini University Hospital, Catanzaro, Italy.
³ Unit of Medical Oncology, Oncology Department, Grand Metropolitan Hospital 'Bianchi Melacrino-Morelli', Reggio Calabria, Italy.
⁴ Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, Palermo University Hospital, Palermo, Italy.
⁵ Unit of Medical Oncology, Oncology Department, 'Pugliese-Ciaccio' Hospital, Catanzaro, Italy.
⁶ Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy. Electronic address: tagliaferri@unicz.it.

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.

Keywords: checkpoints inhibitors; frontline therapy; network meta-analysis; non-small-cell lung cancer; systematic review.

Publication types

Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Immunological* / adverse effects
B7-H1 Antigen
Bevacizumab / therapeutic use
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / pathology
Humans
Ipilimumab / therapeutic use
Lung Neoplasms* / pathology
Nivolumab / therapeutic use

Substances

Antineoplastic Agents, Immunological
B7-H1 Antigen
Ipilimumab
Bevacizumab
Nivolumab