First-line treatment options for advanced non-small cell lung cancer patients with PD-L1 ≥ 50%: a systematic review and network meta-analysis

Abstract

Introduction: Single-agent immune checkpoint inhibitors (ICIs) like pembrolizumab or atezolizumab have been approved as first-line monotherapy for advanced non-small cell lung cancer (NSCLC) patients with PD-L1 ≥ 50%. However, emerging evidences have showed that ICI combinations (chemoimmunotherapy or dual-agent ICIs) argue to offer a higher response rate. In this network meta-analysis, we aimed to evaluate the efficacy and toxicity of first-line single-agent ICIs versus ICI combinations for advanced NSCLC patients with PD-L1 ≥ 50%.

Methods: PubMed, Embase, Cochrane Library and the Clinicaltrials.gov were systematically searched to extract eligible literature until December 2020. Outcomes included overall survival (OS), progression free survival (PFS), objective response rate (ORR) and treatment related adverse events (TRAEs) of grades 3-5.

Results: Fourteen studies with 3448 patients were included. The results showed that chemotherapy plus ICIs significantly improved PFS and ORR compared to chemotherapy, and sinti-chemo (HR: 0.31, 95% CI: 0.20-0.49) and pembro-chemo (OR: 4.2, 95% CI: 2.6-6.7) ranked first. In terms of OS, cemiplimab provided the best benefit versus chemotherapy (HR: 0.57, 95% CI: 0.43-0.77), followed by atezolizumab and pembro-chemo. In the subgroup analysis of histological type, pembro-chemo and sinti-chemo showed the best benefit of PFS in squamous and nonsquamous NSCLC, respectively, while there was no significant difference between ICI combinations with single-agent ICIs in OS. Moreover, the addition of chemotherapy to ICIs elevated toxicity compared to chemotherapy.

Conclusion: The study suggested that chemotherapy plus ICIs might improve PFS and ORR than single-agent ICIs for advanced NSCLC patients with PD-L1 ≥ 50%. However, it did not lead to OS benefit.

Keywords: Immune checkpoint inhibitors; Network meta-analysis; Non-small cell lung cancer; PD-(L)1 inhibitors; PD-L1 high expression.

Fig. 1

Flow diagram for study review and inclusion

Fig. 2

Network plot of multiple therapies in the first-line treatment of advanced NSCLC with PD-L1 ≥ 50%

Fig. 3

Forest plots for advanced non-small cell lung cancer patients with PD-L1 ≥ 50%. a Hazard ratio for overall survival; b hazard ratio for progression free survival; c response ratio for objective response rate; d risk ratio for TRAEs of grades 3–5

Fig. 4

Cumulative ranking probability for different treatments. a Overall survival; b progression free survival; c objective response rate; d TRAEs of grades 3–5

Fig. 5

Forest plots for subgroup. a Overall survival of squamous NSCLC; b progression free survival of squamous NSCLC; c overall survival of nonsquamous NSCLC; d progression free survival of nonsquamous NSCLC