Efficacy and safety of immune checkpoint inhibitors combined with radiotherapy in non-small-cell lung cancer: A meta-analysis with potential clinical predictors.

The combination of immune checkpoint inhibitors (ICIs) and radiotherapy (RT) has shown promise in improving the outcomes in non-small cell lung cancer (NSCLC) patients; however, the potential benefits and predictors remain unclear. This meta-analysis evaluated the efficacy and safety of ICI + RT compared to RT or ICI monotherapy and explored the potential factors influencing the treatment efficacy of this combination therapy. The efficacy was assessed using hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS). Multivariable data were pooled, and subgroup analyses were performed to identify the influencing factors. The safety was evaluated using odds ratios (OR) of any grade and grade ≥3 treatment-related adverse events (TRAEs). ICI + RT significantly improved the OS of patients with brain metastases compared to RT alone (HR = 0.42; P = 0.004). The combination therapy showed improved OS (HR = 0.71; P < 0.001) and PFS (HR = 0.69; P < 0.001) compared to ICI monotherapy. Subgroup analysis revealed significant survival benefits in metastatic and oligometastatic NSCLC patients receiving sequential ICI after RT and those undergoing intracranial or extracranial RT. ICI + RT increased the incidence of any grade TRAEs (OR = 1.3; P = 0.007) compared to ICI alone; no significant difference was observed in grade ≥3 TRAEs. ICI + RT provides significant survival benefits over monotherapy in advanced NSCLC, with a manageable toxicity profile. Prospective trials are needed to validate these findings and refine patient selection for combination therapy.