Optimal drug regimens for squamous non-small cell lung cancer: a systematic review and a Bayesian network...

Current treatment options for patients with squamous non-small cell lung cancer (sqNSCLC) include immune checkpoint inhibitors combined with chemotherapy, monotherapy with immune therapy, and platinum-based doublet chemotherapy, among others. However, there is still a lack of systematic comparisons regarding the relative efficacy and safety of these regimens. This study aims to comprehensively assess the clinical benefits [such as overall survival (OS), progression-free survival (PFS)] and adverse event rates across different treatment strategies via a network meta-analysis, providing evidence-based guidance for individualized treatment decisions in sqNSCLC patients.

We searched PubMed, Embase, Cochrane Library, and Web of Science from inception to May 3, 2025 for eligible randomized controlled trials (RCTs). The primary outcome measures were PFS and OS; secondary outcomes included objective response rate (ORR) and grade ≥3 treatment-related adverse events (≥3 TRAEs). A network meta-analysis was carried out using Stata 16.0 and R 4.4.0.

A total of 32 RCTs, involving 9,652 participants, were included. This study analyzed 18 different treatment strategies. The network meta-analysis showed that for PFS, paclitaxel-based doublet chemotherapy combined with programmed cell death-1 and programmed death-ligand 1 [PD-(L)1] checkpoint inhibitors [surface under the cumulative ranking curve (SUCRA): 96.52%] and gemcitabine-based doublet chemotherapy combined with PD-(L)1 checkpoint inhibitors (SUCRA: 85.16%) were the most effective. For OS, paclitaxel-based doublet chemotherapy combined with a Toll-like receptor-2 agonist (CADI-05) (SUCRA: 92.11%), paclitaxel-based doublet chemotherapy combined with PD-(L)1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors (SUCRA: 89.65%), and paclitaxel-based doublet chemotherapy combined with PD-(L)1 checkpoint inhibitors (SUCRA: 83.58%) were the top three choices. The combination of paclitaxel-based doublet chemotherapy with PD-(L)1 checkpoint inhibitors (SUCRA: 87.00%) was associated with the best improvement in ORR.

For first-line treatment of sqNSCLC, the current evidence supports the use of paclitaxel-based doublet chemotherapy combined with PD-(L)1 checkpoint inhibitors as one of the preferred treatment options. However, more high-quality trials are needed to confirm these findings.