Comparisons of Underlying Mechanisms, Clinical Efficacy and Safety Between Anti-PD-1 and Anti-PD-L1 Immunotherapy: The State-of-the-Art Review and Future Perspectives

Abstract

Over the past decade, diverse PD-1/PD-L1 blockades have demonstrated significant clinical benefit in across a wide range of tumor and cancer types. With the increasing number of PD-1/PD-L1 blockades available in the market, differences between the clinical performance of each of them started to be reported. Here, we provide a comprehensive historical and biological perspective regarding the underlying mechanism and clinical performance of PD-1/PD-L1 blockades, with an emphasis on the comparisons of their clinical efficacy and safety. The real-world evidence indicated that PD-1 blockade may be more effective than the PD-L1, though no significant differences were found as regards to their safety profiles. Future head-to-head studies are warranted for direct comparison between them. Finally, we summarize the yet to be elucidated questions and future promise of anti-PD-1/PD-L1 immunotherapy, including a need to explore novel biomarkers, novel combinatorial strategies, and their clinical use on chronic infection.

Real-world outcomes of regorafenib combined with immune checkpoint inhibitors in patients with advanced or metastatic microsatellite stable colorectal cancer: A multicenter study

“…Previous studies have suggested superior efficacy of PD-1 inhibitors than programmed cell death ligand-1 (PD-L1) inhibitors, while the difference among different PD-1 inhibitors has not been fully elucidated [ 27 ]. Currently, only nivolumab and pembrolizumab have been approved for treating MSI-H colorectal cancer [ 28 ]. Although exploratory analyses detected no significant difference in response and PFS among different PD-1 inhibitors in this study, the heterogenous regimens may exhibit different treatment efficacy and require more investigations.…”

Real-World Analysis of Nivolumab and Atezolizumab Efficacy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

“…Among all types of lung cancer, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases. In recent years, immunotherapy agents, specifically immune checkpoint inhibitors (ICIs) that target programmed death 1 (PD-1) or its ligand (PD-L1), have shown revolutionary benefits against NSCLC, among other solid tumours [ 2 ]. Between 2015 and 2016, three agents, nivolumab, pembrolizumab (anti-PD-1 antibodies) and atezolizumab (anti PD-L1 antibody), were approved for the treatment of advanced NSCLC and are now widely used in clinical practice.…”

PD-L1+ neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab

“…These results suggest that peripheral blood PD-L1 + PMN frequency could represent a novel biomarker of BRAF wild type MPs. Anti-PD-1 monoclonal antibodies, by neutralizing T cell inactivation in the TME, promote an anti-tumor response in different types of cancers, thus improving patient survival ( 32 ). However, a proportion of patients still do not respond or progress after initial therapy ( 3 ), underscoring the need to delve deeper into the immunological mechanisms responsible for this lack of response.…”