Efficacy and Safety of PD-1/PD-L1 Checkpoint Inhibitors versus Anti-PD-1/PD-L1 Combined with Other Therapies for Tumors: A Systematic Review

Abstract

Objective: In recent years, the anti-programmed cell death protein-1 and its ligand (PD-1/PD-L1) or combination therapies have been recommended as an alternative emerging choice of treatment for oncology patients. However, the efficacy and adverse events of different combination strategies for the treatment of tumors remain controversial. Methods: PubMed, Embase, Cochrane Library, the American Society of Clinical Oncology (ASCO), and the European Society of Medicine Oncology (ESMO) were searched from database inception until 16 February 2022. The endpoints of objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were analyzed from different treatment schemes and tumor types. The protocol was registered in PROSPERO (CRD42022328927). Results: This meta-analysis included forty-eight eligible studies. Combination therapy has improved ORR (RR = 1.40, p < 0.001), DCR (RR = 1.22, p < 0.001), and PFS (the median survival ratio (MSR) was estimated to be 1.475 p < 0.001) compared to anti-PD-1/PD-L1 but had no significant benefit on OS (MSR was estimated to be 1.086 p = 0.117). Besides, combination treatment strategies are more toxic in any grade AEs (RR = 1.13, p < 0.001) and grade 3–5 AEs (RR = 1.81, p < 0.001). Conclusions: Treatment with PD-1/PD-L1 inhibitors in combination with other antitumor therapies improve patients’ ORR, DCR, and PFS compared to anti-PD-1/PD-L1. However, it is regrettable that there is no benefit to OS and an increased risk of AEs in combinatorial therapies.

Difference between Keratinized- and Non-Keratinized-Originating Epithelium in the Process of Immune Escape of Oral Squamous Cell Carcinoma

“…Blockade of the PD-1/PD-L1 axis is already used in clinical practice using several antibody drugs [11,12,16], and more than 100 clinical studies are ongoing [24]. Current clinical studies show a strong relationship between the PD-L1 expression level and clinical efficacy [12].…”

“…In the cancer immunoediting system, the PD-1/programmed cell death 1 ligand 1 (PD-L1) plays a central role [13]. PD-1 is the major receptor in immune cells as an activated checkpoint in the immune system and is expressed in T cells, B cells and natural killer cells activated in the tumor microenvironment [14][15][16]. PD-L1 is a PD-1 ligand that induces the phosphorylation of two motifs in PD-1.…”

“…PD-L1 is a PD-1 ligand that induces the phosphorylation of two motifs in PD-1. This interaction inhibits the proliferation and response of T cells; then, PD-L1 and PD-1 signaling is called the "Do not kill me signal" [16]. Another immune checkpoint molecule, Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), is also focused on the development of ICIs [7].…”

Novel SPEA Superantigen Peptide Agonists and Peptide Agonist-TGFαL3 Conjugate. In Vitro Study of Their Growth-Inhibitory Effects for Targeted Cancer Immunotherapy

“…The focus has been on utilizing the patient’s immune system to find and destroy cancer cells with little or no harm to the healthy ones. Recently several immunotherapy strategies have been developed, such as immune checkpoint inhibitors, Anti-CTLA-4 antibodies, Anti-PD-1 drugs, and Anti-PD-L-1 drugs [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ], chimeric antigen receptor T-cells, or CAR-T [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”