Immune checkpoint inhibitors (ICI) in combination with chemotherapy as first-line (1L) treatment for non-small cell lung cancer (NSCLC): A pair-wise meta-analysis (MA)

Abstract

Background: ICI has revolutionized the treatment of lung cancer, with new approaches in 1L NSCLC. The aim of this study is to compare the efficacy of treatments that combine chemotherapy (CH) plus a PD1/L1 inhibitor in clinical trials (CT) and the benefits in the different subgroups of patients. Methods: We performed a searching in Pubmed to identify CT. Key words were: NSCLC, PD1/L1 and CH. All phase III trials that combined CH with an antiPD1/L1 were selected. The results were combined in MA with the corresponding forest plots and presented as Hazard Ratios (HR) and Odds Ratio (OR), with 95% CI. DerSimonian-Laird random effects models for main and subgroup analyses has been implemented. Results: A total of 86 publications were reviewed, 6 of them met the inclusion criteria with 3,807 patients. 6 pair wise MA was performed. Control arm in all studies was platinum doublet CH. Bevacizumab was added in 1 trial in the control and experimental arm. 4 studies tested an antiPD-1, and 2 antiPD-L1. 2 studies included EGFR/ALK mutated patients (EGFR/ALK+). PFS final data was reported in all the studies and overall survival (OS) in 4. The addition of PD-1/L1 inhibitors was associated with significantly prolonged progression-free survival (PFS) (HR: 0.59, 95% CI: 0.55-0.64, p<0.001) and OS (HR: 0.75, 95CI: 0.64-0.87; p<0.001). Women,≤65 years old, PS 0, never smokers, liver metastasis (mx) and PD-L1 ≥50% were the subgroups with better benefit (table). Just one trial showed PFS and OS improvement in EGFR/ALK+. Numerically better ORR was obtained in the IMpower150 (56.4%) trial for non-squamous (sq) NSCLC and KEYNOTE407 for sq NSCLC (57.9%). Conclusion: The association of immunotherapy plus CH is a better treatment option for all patients in 1L NSCLC. Standard subgroups are the most benefited, except liver mx patients and EGFR/ALK+ especially benefited for the combination of an antiPD-L1 and an antiVEGF. (Table Presented) .