A meta-analysis of efficacy and safety of antibodies targeting PD-1/PD-L1 in treatment of advanced nonsmall cell lung cancer

Abstract

Background: Nonsmall cell lung cancer (NSCLC)-patients treated with standard chemotherapy experienced progression rapidly. A novel therapy based on programed death 1 (PD-1)/programed death ligand 1 (PD-L1) inhibitors showed an increasing potential in several malignancies including advanced NSCLC.

Objectives: This article is a meta-analysis aiming to systematically evaluate the efficacy and safety profiles of PD-1/PD-L1 agents in patients with NSCLC.

Data sources: Data were collected from eligible studies searched from PubMed, ScienceDirect, and Web of Science.

Synthesis methods: Pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was estimated to assess the efficacy of PD-1/PD-L1 inhibitors versus docetaxel, pooled odds ratio (OR) was calculated for objective response rate (ORR). The overall frequency was estimated for 1-year OS, 1-year progression-free survival, and ORR. A subgroup analysis among NSCLC patients tested with different epidermal growth factor receptor (EGFR) status was also performed to figure out the relationship between EGFR status and efficacy of PD-1/PD-L1 therapies. OR for occurrence of any grade and grade 3 to 5 treatment-related adverse effect was calculated for evaluating the safety of PD-1/PD-L1 therapies.

Results: Nine studies were included in this analysis. The pooled HRs for OS and PFS were 0.68 (95% confidence interval [CI] 0.61-0.75) and 0.83 (95% CI 0.75-0.91), respectively, the pooled OR for ORR was 1.83 (95% CI 1.41-2.36), indicating a significant improvement in OS, PFS, and ORR. In the results of subgroup analysis, the HR for OS in NSCLC patients was 1.05 (95% CI 0.69-1.59) in patients with mutant EGFR and 0.66 (95% CI 0.57-0.77) in patients with wild-type EGFR status. OR for occurrence was 0.36 (95% CI 0.28-0.46) in any grade treatment-related adverse effect and 0.18 (95% CI 0.14-0.22) in grade 3 to 5 treatment-related adverse effect, suggesting a superior safety profile of PD-1/PD-L1 inhibitors.

Conclusion: The PD-1/PD-L1 therapy significantly prolonged the OS and improved the ORR, simultaneously lowering the treatment-related adverse effect events versus docetaxel.

Figure 1

Flowchart of study selection procedure.

Figure 2

Pooled hazard ratio for overall survival (A), progression-free survival (B), and pooled odds ratio for objective response rate (C) in patients treated with programed death 1/programed death ligand 1 agents versus docetaxel. ∗ Represents an arm treated with pembrolizumab 10 mg/kg in Ref. ^[18].

Figure 3

Subgroup analysis of overall survival in patients with different epidermal growth factor receptor status.

Figure 4

Overall 1-year overall survival (A), 1-year progression-free survival (B), and ORR (C) in patients administrated with programed death 1/programed death ligand 1 agents as monotherapy.

Figure 5

Pooled odds ratio for incidence of any grade treatment-related adverse effect (A) and grade 3 to 5 treatment-related adverse effect (B).