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Research Status and Outlook of PD-1/PD-L1 Inhibitors for Cancer Therapy.

ABSTRACT: PD-1/PD-L1 inhibitors are a group of immune checkpoint inhibitors as front-line treatment of multiple types of cancer. However, the serious immune-related adverse reactions limited the clinical application of PD-1/PD-L1 monoclonal antibodies, despite the promising curative effects. Therefore, it is urgent to develop novel inhibitors, such as small molecules, peptides or macrocycles, targeting the PD-1/PD-L1 axis to meet the increasing clinical demands. Our review discussed the mechanism of action of PD-1/PD-L1 inhibitors and presented clinical trials of currently approved PD-1/PD-L1 targeted drugs and the incidence of related adverse reactions, helping clinicians pay more attention to them, better formulate their intervention and resolution strategies. At last, some new inhibitors whose patent have been published are listed, which provide development ideas and judgment basis for the efficacy and safety of novel PD-1/PD-L1 inhibitors.

SUBMITTER: Ai L

PROVIDER: S-EPMC7490077 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Research Status and Outlook of PD-1/PD-L1 Inhibitors for Cancer Therapy.

Ai Leilei L Chen Jian J Yan Hao H He Qiaojun Q Luo Peihua P Xu Zhifei Z Yang Xiaochun X

Drug design, development and therapy 20200908

PD-1/PD-L1 inhibitors are a group of immune checkpoint inhibitors as front-line treatment of multiple types of cancer. However, the serious immune-related adverse reactions limited the clinical application of PD-1/PD-L1 monoclonal antibodies, despite the promising curative effects. Therefore, it is urgent to develop novel inhibitors, such as small molecules, peptides or macrocycles, targeting the PD-1/PD-L1 axis to meet the increasing clinical demands. Our review discussed the mechanism of actio ...[more]

PMID: 32982171

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Project description:OBJECTIVE:To evaluate the relative efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors versus conventional drugs in patients with cancer that were PD-L1 positive and PD-L1 negative. DESIGN:Meta-analysis of randomised controlled trials. DATA SOURCES:PubMed, Embase, Cochrane database, and conference abstracts presented at the American Society of Clinical Oncology and European Society of Medical Oncology up to March 2018. REVIEW METHODS:Studies of PD-1 or PD-L1 inhibitors (avelumab, atezolizumab, durvalumab, nivolumab, and pembrolizumab) that had available hazard ratios for death based on PD-L1 positivity or negativity were included. The threshold for PD-L1 positivity or negativity was that PD-L1 stained cell accounted for 1% of tumour cells, or tumour and immune cells, assayed by immunohistochemistry staining methods. RESULTS:4174 patients with advanced or metastatic cancers from eight randomised controlled trials were included in this study. Compared with conventional agents, PD-1 or PD-L1 inhibitors were associated with significantly prolonged overall survival in both patients that were PD-L1 positive (n=2254, hazard ratio 0.66, 95% confidence interval 0.59 to 0.74) and PD-L1 negative (1920, 0.80, 0.71 to 0.90). However, the efficacies of PD-1 or PD-L1 blockade treatment in patients that were PD-L1 positive and PD-L1 negative were significantly different (P=0.02 for interaction). Additionally, in both patients that were PD-L1 positive and PD-L1 negative, the long term clinical benefits from PD-1 or PD-L1 blockade were observed consistently across interventional agent, cancer histotype, method of randomisation stratification, type of immunohistochemical scoring system, drug target, type of control group, and median follow-up time. CONCLUSIONS:PD-1 or PD-L1 blockade therapy is a preferable treatment option over conventional therapy for both patients that are PD-L1 positive and PD-L1 negative. This finding suggests that PD-L1 expression status alone is insufficient in determining which patients should be offered PD-1 or PD-L1 blockade therapy.

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Research Status and Outlook of PD-1/PD-L1 Inhibitors for Cancer Therapy.

Publications

Research Status and Outlook of PD-1/PD-L1 Inhibitors for Cancer Therapy.

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