Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50%

Abstract

Background: For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic literature review and network meta-analysis (NMA) was conducted to identify/compare the efficacy/safety of cemiplimab versus pembrolizumab or other immune-oncology monotherapies from randomized-controlled trials (RCTs) published in November 2010–2020. Methods: Relevant RCTs were identified by searching databases and conference proceedings as per ISPOR, NICE, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR) and safety/tolerability. Fixed-effect models were used due to limited evidence. Various sensitivity analyses were conducted to validate the base case analyses. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded because an incompatible PD-L1 assay (SP142) was used for patient selection. For first-line advanced NSCLC with PD-L1 ⩾50%, cemiplimab was associated with statistically significant improvements in PFS [HR (95% credible interval [CrI]): 0.65 (0.50–0.86), 1–12 months] and ORR [odds ratio (OR) (95% CrI): 1.64 (1.04–2.62)], and comparable OS [HR (95% CrI): 0.77 (0.54–1.10), 1–12 months] versus pembrolizumab. There was no evidence of differences between cemiplimab and pembrolizumab for Grade 3–5 adverse events (AEs) [OR (95% CrI): 1.47 (0.83–2.60)], immune-mediated AEs [1.75 (0.33–7.49)], and all-cause discontinuation due to AEs [1.21 (0.58–2.61)]. Conclusions: Considering the limitations of indirect treatment comparisons, in patients with advanced NSCLC and PD-L1 ⩾50%, cemiplimab monotherapy demonstrated significant improvements in PFS and ORR, comparable OS, and no evidence of differences in safety/tolerability versus pembrolizumab.

First-line immunotherapy efficacy in advanced squamous non-small cell lung cancer with PD-L1 expression ≥50%: a network meta-analysis of randomized controlled trials

“…In a network meta-analysis evaluating PD-(L)1 inhibitors as monotherapy for first-line treatment in NSCLC patients with high PD-L1 expression, researchers identified cemiplimab as the top-ranking agent for OS, followed by atezolizumab and pembrolizumab ( 42 ). In another network meta-analysis assessing immune monotherapy as a first-line treatment for advanced NSCLC patients with PD-L1 expression ≥50%, researchers found that cemiplimab and pembrolizumab exhibited favorable performance in terms of progression-free survival, overall survival, and overall response rate (ORR) ( 44 ). In our current study, cemiplimab also demonstrated favorable performance in OS (HR, 0.48; 95% CI, 0.30–0.77).…”

Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1: Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer

“…In a recent network meta-analysis of immunotherapies in first-line advanced NSCLC with PD-L1 ≥50% ( 4 ), the base case results comparing EMPOWER-Lung 1 ( 1 ), KEYNOTE-024 ( 5 ), and KEYNOTE-042 ( 6 ) demonstrated cemiplimab was associated with comparable OS and statistically significant improvements in progression-free survival from 6–30 months versus pembrolizumab. No statistically significant differences in the incidence of grade 3–5 adverse events (AEs), grade 3–5 immune-mediated AEs, and all-cause discontinuations due to AEs were observed between the two treatments.…”