Real-world effectiveness of pembrolizumab for first-line treatment of metastatic non-small-cell lung cancer: a decade of evidence and experience

Non-small cell lung cancer (NSCLC) remains a global burden, particularly due to late‑stage diagnosis. Immune checkpoint inhibitors (ICIs) for mNSCLC, including first-line (1L) pembrolizumab regimens, significantly improved survival for these patients, establishing them as the current standard of care (SoC). Since the approvals of pembrolizumab, a large volume of real-world evidence (RWE) has been published across patient populations and with long-term follow-ups. This narrative review evaluates the available RWE on PubMed and Embase, assessing real-world clinical outcomes from 2016 to 2026 against pembrolizumab (KEYNOTE) clinical trials. Across geographies and practice settings, RWE for 1L pembrolizumab in mNSCLC is supportive of KEYNOTE findings, with survival outcomes comparable to the trials. Among heterogeneous populations, older age did not alter outcomes; however, cohorts with higher performance scores expectedly experienced poorer outcomes. Global treatment patterns highlighted pembrolizumab-containing regimens as the most administered ICI, affirming its role as SoC in 1L mNSCLC treatment. The volume of RWE studies, long-term follow-up data, and consistency in results observed across regions and diverse patient populations reinforce the use of pembrolizumab regimens as 1L SoC for patients with mNSCLC. Further analysis on the impact of heterogeneous subpopulations on the efficacy of pembrolizumab would be beneficial to support evidence-based decision-making.