Addition of Immune Checkpoint Inhibitors to Chemotherapy vs Chemotherapy Alone as First-Line Treatment in Extensive-Stage Small-Cell Lung Carcinoma: A Systematic Review and Meta-Analysis

Edurne Arriola 1, María González-Cao 2, Manuel Domine 3, Javier De Castro 4, Manuel Cobo 5, Reyes Bernabé 6, Alejandro Navarro 7, Ivana Sullivan 8, José Manuel Trigo 9, Joaquín Mosquera 10, Leonardo Crama 11, Dolores Isla 12

Affiliations 

• PMID: 35032007
 
• DOI: 10.1007/s40487-021-00182-0

Abstract

Introduction: The addition of immune checkpoint inhibitors (ICIs) to conventional chemotherapy (CT) as first-line treatment improves survival in extensive-stage small-cell lung cancer (ES-SCLC). The aim of this meta-analysis was to determine the relative efficacy of first-line ICIs compared with CT in patients with ES-SCLC.

Methods: Two independent reviewers extracted relevant data according to PRISMA guidelines and assessed the risk of bias using the Cochrane Collaboration's risk-of-bias tool. Meta-analysis was conducted using random-effects models to calculate an average effect size for overall survival (OS), progression-free survival (PFS), and safety outcomes in the overall populations and clinically relevant subgroups.

Results: A literature search of PubMed and Embase was performed. Six randomized controlled clinical trials (IMpower133, CHECKMATE-451, CASPIAN, KEYNOTE-604, and phase II and III ipilimumab plus CT trials) with a total of 3757 patients were included. Compared with CT alone, ICIs plus CT showed a favourable effect on OS (hazard ratio [HR] 0.85; 95% confidence intervals [CI] 0.79-0.96) and PFS (HR 0.78; 95% CI 0.72-0.83) but a non-significant increase in the risk of experiencing any adverse event (relative risk, 1.05; 95% CI 0.99-1.11). The estimated HR for OS favoured ICI combinations in all planned subgroups according to age (< 65 years/≥ 65 years), sex (men/women), and ECOG performance status (0/1). Analysis by specific ICI revealed significant improvements in OS only for atezolizumab + CT (HR 1.36; 95% CI 1.09-1.69) and durvalumab + CT (HR 1.35; 95% CI 1.12-1.62) compared with CT alone.

Conclusion: Combining anti-programmed cell death ligand 1 antibodies with platinum/etoposide is a superior therapeutic approach compared to CT alone for the first-line treatment of patients with ES-SCLC.

Keywords: Anti-PD-1/PD-L1 antibodies; Chemotherapy; Immunotherapy; Meta-analysis; Small cell lung carcinoma.

© 2022. The Author(s).