(C-226) Efficacy and Safety of Immune Checkpoint Inhibitors as First-Line Treatment for Advanced Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.

Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide, with standard treatments such as surgery, chemotherapy, radiotherapy, and targeted therapy often yielding limited efficacy. Recently, immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic strategy, significantly enhancing survival outcomes in advanced NSCLC. This study aims to identify the most effective first-line ICI-based regimen (excluding bevacizumab), irrespective of PD-L1 expression levels.

Objective: To evaluate the comparative efficacy and safety of ICIs as first-line therapy in advanced non-small cell lung cancer (NSCLC).

Methods: A systematic review and frequentist network meta-analysis (NMA) were conducted following PRISMA guidelines and registered in PROSPERO (CRD42024616245). Phase II and III randomized controlled trials were identified through PubMed, Embase, and Google Scholar. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes included the objective response rate (ORR) and adverse events (AEs). Treatments were ranked by Surface Under the Cumulative Ranking (SUCRA) and validated by a league table. Publication bias was assessed using a funnel plot and Egger’s test. Risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool.

Results: Thirty-one studies involving 15,172 patients were included, evaluating 21 ICI-based regimens irrespective of PD-L1 expression. For OS and PFS, Prolgolimab plus chemotherapy (hazard ratio [HR]: 0.51, 95% CI: 0.35–0.74; SUCRA: 91%) and Penpulimab plus chemotherapy (HR: 0.43, 95% CI: 0.32–0.58; SUCRA: 91%) demonstrated the most favorable outcomes, respectively. Pembrolizumab plus chemotherapy showed the highest ORR (odds ratio [OR]: 3.10, 95% CI: 2.18–4.41; SUCRA: 86%) compared to chemotherapy alone. In subgroup analyses, Prolgolimab plus chemotherapy ranked highest for OS in both PD-L1 ≥50% and ≤1% cohorts. For PFS, Penpulimab plus chemotherapy and Serplulimab plus chemotherapy ranked highest for PD-L1 ≥50% and ≤1%, respectively. Atezolizumab monotherapy was associated with the lowest incidence of any-grade and grade ≥3 AEs.

Conclusions: Our comprehensive analysis suggests that Prolgolimab and Penpulimab regimens offer superior survival benefits compared to chemotherapy alone, although the combination therapies have higher AEs. The optimal treatment strategy depends entirely on patient characteristics and PD-L1 expression.