Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis

• Published in: BMJ (Online) Vol. 362; p. k3529
• Main Authors: Shen, Xian, Zhao, Bin
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 10.09.2018; BMJ Publishing Group Ltd
• Subjects: Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - therapeutic use; Apoptosis; B7-H1 Antigen - administration & dosage; B7-H1 Antigen - therapeutic use; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - secondary; Cell death; Clinical medicine; Clinical trials; Humans; Immunohistochemistry; Immunosuppressive agents; Immunotherapy; Immunotherapy - methods; Ligands; Lung cancer; Medical prognosis; Meta-analysis; Metastases; Monoclonal antibodies; Neoplasm Metastasis - drug therapy; Neoplasms - drug therapy; Nivolumab - administration & dosage; Nivolumab - therapeutic use; Patients; PD-1 protein; PD-L1 protein; Pembrolizumab; Programmed Cell Death 1 Receptor - drug effects; Randomized Controlled Trials as Topic; Survival Analysis; Systematic review; Targeted cancer therapy; Treatment Outcome; Tumors
• ISSN: 0959-8138; 1756-1833
• DOI: 10.1136/bmj.k3529

AbstractObjectiveTo 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.DesignMeta-analysis of randomised controlled trials.Data sourcesPubMed, 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 methodsStudies 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.Results4174 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.ConclusionsPD-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.