First-line Pembrolizumab Versus Pembrolizumab Plus Chemotherapy Versus Chemotherapy Alone in Non-small-cell Lung Cancer: A Systematic Review and Network Meta-analysis

Abstract

Background: This study aimed to comprehensively review the available evidence regarding the efficacy of first-line pembrolizumab for advanced/metastatic non-small-cell lung cancer (NSCLC), and to compare pembrolizumab monotherapy versus pembrolizumab plus chemotherapy versus chemotherapy alone.

Materials and methods: A search of the PubMed, EMBASE, and Cochrane Library databases was performed in July 2018, and abstracts from the American Society of Clinical Oncology meetings (2015-2018) were reviewed. Summaries of the results were pooled using a random-effect model to determine the pooled hazard ratio (HR) for progression-free survival (PFS), overall survival (OS), and their 95% confidence intervals (CIs). A network meta-analysis was used to indirectly compare pembrolizumab monotherapy with pembrolizumab plus chemotherapy.

Results: A total of 4 relevant phase III trials comprising 2754 patients were identified. Pembrolizumab (with or without chemotherapy) led to significant improvements in OS and PFS, irrespective of the programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS). In particular, for the subgroup with PD-L1 TPS ≥ 50%, the HR of PFS was 0.49 (95% CI, 0.32-0.76; P = .001), and that of OS was 0.57 (95% CI, 0.45-0.73; P < .001). In terms of PFS, pembrolizumab plus chemotherapy was superior to pembrolizumab monotherapy with an HR of PFS 0.52 (95% CI, 0.27-0.99; P = .048) for the subgroup with PD-L1 TPS ≥ 50%.

Conclusions: For patients with NSCLC with PD-L1 TPS ≥ 50%, pembrolizumab plus chemotherapy has a better PFS than pembrolizumab monotherapy in this meta-analysis. To confirm this finding, a prospective phase III trial that directly compares the treatments is warranted.

Keywords: Immunotherapy; Meta-analysis; Network meta-analysis; Non-small cell lung cancer; Pembrolizumab.