In addition to its central role as a key element of current immunotherapy strategies, PD-L1 has emerged as a potential prognostic factor and biomarker to predict which patients are more likely to respond to immunotherapy in NSCLC.

The binding of PD-L1 to its receptor PD-1 on activated T cells can lower the T-cell immune responses and prevent elimination of tumor cells. PD-L1 is expressed on tumor cells (TCs) and tumor-infiltrating immune cells (ICs). In this regard, immunotherapy targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has markedly improved the overall survival (OS) of patients, not only in those with metastatic NSCLC, but also in patients with locally advanced disease and extensive-stage small-cell lung cancer. Major progress was made with the emergence of the immunotherapy with reduced overall toxicity and almost complete absence of non-specific side effects compared to chemotherapy and other classic cancer therapies, but with specific toxicity profiles depending on the mechanisms of action.

Since then, the understanding of the biology of this cancer has rapidly increased and the use of targeted therapy with tyrosine kinase inhibitors (TKIs) improve the management of patients with oncogenic driven cancers and their survival rates. Its prognosis is poor, with five-year survival rates of 0–5% with the use of chemotherapy, which has been the only systemic therapeutic strategy available for decades. Non-small cell lung cancer (NSCLC), the most frequent lung carcinoma, accounts for 85% of all diagnosed cases and is frequently detected in the advanced stages. Lung cancer is the leading cause of cancer death among men, and the second among women worldwide. Evaluations with longer follow up are still needed to determine the superiority of any specific drug. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs.

In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HR pooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HR pooled = 0.69, 95% CI: 0.61–0.78 p < 0.001) and overall response rate (ORR) (Risk ratio (RR) pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). Six clinical trials with 2111 patients were included. To that end, we conducted a systematic review. We also evaluated efficacy outcomes according to tumor mutational burden (TMB).

In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC).

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