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Abstract
BackgroundPD-1/PD-L1 inhibitors have been implicated as potentially effective anti-cancer therapies. Some clinical randomized controlled trials (RCTs) have been completed for a variety of PD-1/PD-L1 inhibitors to treat various malignancies, and more RCTs are still under way. We carried out this systematic meta-analysis to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors.MethodsWe searched PubMed, EMBASE, clinical trial registers, conference reports, and related reviews. Eligible RCTs that compared PD-1/PD-L1 inhibitors with other chemotherapy agents or placebo in solid tumor patients were included. For each RCT, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), stable disease rate (SDR), progressive disease rate (PDR), and adverse events (AEs) were pooled for meta-analysis.FindingsBased on an analysis of 10 eligible RCTs, PD-1/PD-L1 inhibitors were found to significantly improve PFS (Hazard ratio (HR), 0.65; 95% confidence interval (CI) 0.53 to 0.79, P<0.001), OS (HR, 0.69; 95%CI 0.62 to 0.76, P<0.001), and ORR (Risk Ratio (RR) 292; 95% confidence interval (CI) 2.06 to 4.15, P<0.00001) in all populations, including melanoma and NSCLC subgroups. However, they failed to increase the DCR of cancer patients (RR 1.15; 95%CI 0.91 to 1.45, P=0.25). Furthermore, less AEs were observed in the PD-1/PD-L1 inhibitor groups than the control groups.InterpretationPD-1 inhibitors are more effective for improving the PFS, OS, and ORR of cancer patients with little toxicity, despite having little effect on increasing of the DCR.
Highlights
Escape from immune surveillance is an important characteristic of carcinoma [1]
The results show that programmed death-1 receptor (PD-1) inhibitors could increase the Objective response rate (ORR) of melanoma patients compared with the control groups (RR 2.89; 95%confidence interval (CI) 2.02 to 4.13; P < 0.00001) (Figure 3A)
The progression-free survival (PFS) and overall survival (OS) of cancer patients treated with PD-1 inhibitors were improved significantly
Summary
Escape from immune surveillance is an important characteristic of carcinoma [1]. The development of therapies to enhance tumor immunity has become an important target for cancer treatment strategies [2]. Immune checkpoint inhibitors have achieved remarkable progress in tumor treatment, and two vital checkpoint www.impactjournals.com/oncotarget receptors, CTLA-4 and the programmed death-1 receptor (PD-1), have been studied most extensively in clinical cancer immunotherapy [3, 4]. These receptors play significant roles in regulating the immune response against malignancy. Some clinical randomized controlled trials (RCTs) have been completed for a variety of PD-1/PD-L1 inhibitors to treat various malignancies, and more RCTs are still under way We carried out this systematic meta-analysis to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors
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