Comparing PD-1/PD-L1 Inhibitors in First-Line Setting of NSCLC

By: Noah Levine
Posted: Monday, March 10, 2025

It is well known that immune checkpoint inhibitors (ICIs)—particularly PD-1/PD-L1 inhibitors—are a key part of the evolving treatment landscape for advanced non–small cell lung cancer (NSCLC). However, finding the optimal first-line treatment approach remains a challenge for many clinicians. In a recent article published in Frontiers in Pharmacology, Ying-Jie Su, PhD, of the Shanghai Jiao Tong University School of Medicine, and colleagues evaluated the efficacy and safety of these inhibitors in first-line treatment settings.

“It can be observed that the recently introduced therapeutic agents appear to demonstrate enhanced efficacy,” the investigators noted.

The researchers analyzed data from 29 phase III randomized controlled trials including 18,885 patients. They compared monotherapies and combination regimens involving PD-1/PD-L1 inhibitors and categorized the treatment outcomes based on overall survival, progression-free survival, objective response rate, and treatment-related adverse events.

The treatment regimen with the best results based on survival outcomes was penpulimab plus chemotherapy. This was followed by camrelizumab plus chemotherapy and sugemalimab plus chemotherapy. The researchers also noted that treatments including any of the available PD-1/PD-L1 inhibitors achieved superior outcomes compared with chemotherapy alone.

Although the investigators provided a “preferred ranking probability for each treatment to determine which treatment option ranks best among all of our options, different results were seen when subgroup analyses of treatment regimens were performed for patients grouped by PD-L1 expression level.” For patients with PD-L1 expression of at least 50%, camrelizumab plus chemotherapy was the most effective regimen. For patients with PD-L1 expresssion between 1% and 49%, cemiplimab plus chemotherapy provided the best overall survival benefit; for patients with PD-L1 expression less than 1%, nivolumab plus ipilimumab was the preferred option. In their review of the safety of the various treatment approaches, the researchers found that PD-1/PD-L1 monotherapies including nivolumab, pembrolizumab, cemiplimab, atezolizumab, and durvalumab were associated with lower rates of grade ≥ 3 treatment-related adverse events compared with combination regimens.

Disclosure: For full disclosures of the study authors, visit www.frontiersin.org.

Frontiers in Pharmacology

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