Which treatment is preferred for advanced non-small-cell lung cancer with wild-type epidermal growth factor receptor in second-line therapy? A meta-analysis comparing immune checkpoint inhibitor, tyrosine kinase inhibitor and chemotherapy.

Di Wu,Chongyang Duan,Liyong Chen,Size Chen,Fenfang Wu

doi:10.18632/oncotarget.20281

Abstract

BackgroundThe recommendations regarding the optimum treatment for advanced non-small-cell lung cancer (NSCLC) patients with wild-type (WT) epidermal growth factor receptor (EGFR) tumors remain unclear. This meta-analysis was conducted to assess the efficacy among programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) antibody, EGFR-tyrosine kinase inhibitors (TKI) and chemotherapy in second-and third-line therapy.Patients and methodsRandomized trials investigating two of the three treatments were searched and included. Multiple treatments comparison and pairwise comparison were performed to assess overall survival (OS) and progression-free survival (PFS), expressed as hazard ratios (HRs). The effect of prespecified study-level characteristics was assessed by subgroup analysis and meta-regression.Results12 randomized trials accruing 3341 advanced patients with WT EGFR tumors were analyzed. PD-1/PD-L1 antibody was associated with significantly longer OS and PFS than chemotherapy (OS: HR 0.67, 95% CrI 0.60–0.75; PFS: HR 0.83, 95% CrI 0.73–0.95) and TKI (OS: HR 0.59, 95% CrI 0.50–0.70; PFS: HR 0.75, 95% CrI 0.66–0.84) , while chemotherapy was associated with significantly longer OS (HR 0.88, 95% CrI 0.77–0.99) and PFS (HR 0.75, 95% CrI 0.66–0.84) than TKI.ConclusionsFor advanced NSCLC patients with WT-EGFR tumors in second- or third-line therapy, PD-1/PD-L1 antibody appeared to be the most efficacious treatment, which was followed by chemotherapy. EGFR-TKI was worse than chemotherapy.

Highlights

Worldwide, lung cancer is the leading cause of cancer mortality, making up about 19% of all cancerrelated deaths [1]
programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) antibody was associated with significantly longer overall survival (OS) and progression-free survival (PFS) than chemotherapy (OS: hazard ratios (HRs) 0.67, 95% credible intervals (CrIs) 0.60–0.75; PFS: HR 0.83, 95% CrI 0.73–0.95) and tyrosine kinase inhibitors (TKI) (OS: HR 0.59, 95% CrI 0.50–0.70; PFS: HR 0.75, 95% CrI 0.66–0.84), while chemotherapy was associated with significantly longer OS (HR 0.88, 95% CrI 0.77–0.99) and PFS (HR 0.75, 95% CrI 0.66–0.84) than TKI
For advanced non-small-cell lung cancer (NSCLC) patients with WT-epidermal growth factor receptor (EGFR) tumors in secondor third-line therapy, PD-1/PD-L1 antibody appeared to be the most efficacious treatment, which was followed by chemotherapy

Summary

Introduction

Lung cancer is the leading cause of cancer mortality, making up about 19% of all cancerrelated deaths [1]. EGFRTKI is recommended as standard first-line treatment www.impactjournals.com/oncotarget for this drug-sensitive subgroup [12]. These mutations occur in only about 15% of White and Africa America patients and mostly 50% of Asian patients. The recommendations regarding the optimum treatment for advanced non-small-cell lung cancer (NSCLC) patients with wild-type (WT) epidermal growth factor receptor (EGFR) tumors remain unclear. This meta-analysis was conducted to assess the efficacy among programmed death-ligand 1 (PD-L1)/ programmed death-1 (PD-1) antibody, EGFR-tyrosine kinase inhibitors (TKI) and chemotherapy in second-and third-line therapy

Methods

Results

Conclusion