Dataset Information

PD-L1 and Survival in Solid Tumors: A Meta-Analysis.

ABSTRACT:

Background

Numerous agents targeting PD-L1/PD-1 check-point are in clinical development. However, the correlation between PD-L1 expression and prognosis of solid tumor is still in controversial. Here, we elicit a systematic review and meta-analysis to investigate the potential value of PD-L1 in the prognostic prediction in human solid tumors.

Methods

Electronic databases were searched for studies evaluating the expression of PD-L1 and overall survival (OS) of patients with solid tumors. Odds ratios (ORs) from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed.

Results

A total of 3107 patients with solid tumor from 28 published studies were included in the meta-analysis. The median percentage of solid tumors with PD-L1 overexpression was 52.5%. PD-L1 overexpression was associated with worse OS at both 3 years (OR = 2.43, 95% confidence interval (CI) = 1.60 to 3.70, P < 0.0001) and 5 years (OR = 2.23, 95% CI = 1.40 to 3.55, P = 0.0008) of solid tumors. Among the tumor types, PD-L1 was associated with worse 3 year-OS of esophageal cancer, gastric cancer, hepatocellular carcinoma, and urothelial cancer, and 5 year-OS of esophageal cancer, gastric cancer and colorectal cancer.

Conclusions

These results suggest that expression of PD-L1 is associated with worse survival in solid tumors. However, the correlations between PD-L1 and prognosis are variant among different tumor types. More studies are needed to investigate the clinical value of PD-L1 expression in prognostic prediction and treatment option.

SUBMITTER: Wu P

PROVIDER: S-EPMC4483169 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

PD-L1 and Survival in Solid Tumors: A Meta-Analysis.

Wu Pin P Wu Dang D Li Lijun L Chai Ying Y Huang Jian J

PloS one 20150626 6

<h4>Background</h4>Numerous agents targeting PD-L1/PD-1 check-point are in clinical development. However, the correlation between PD-L1 expression and prognosis of solid tumor is still in controversial. Here, we elicit a systematic review and meta-analysis to investigate the potential value of PD-L1 in the prognostic prediction in human solid tumors.<h4>Methods</h4>Electronic databases were searched for studies evaluating the expression of PD-L1 and overall survival (OS) of patients with solid t ...[more]

PMID: 26114883

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Project description:Blocking the Programmed Cell Death Protein 1 (PD-1)/programmed death ligand-1 (PD-L1) axis has demonstrated great efficacy in cancer immunotherapy treatment and remains the central modality of immune targeting. To support the rational and tailored use of these drugs, it is important to identify reliable biomarkers related to survival. The role of the soluble form of the PD-L1 (sPD-L1) as a prognostic biomarker related to survival in solid cancer patients treated with immunotherapy has not yet been consistently evaluated. A systematic literature search of original articles in PubMed, MEDLINE and Scopus was conducted. Studies reporting hazard ratios (HRs) with a 95% confidence interval (CI) or Kaplan–Meier curves or individual patient data for overall survival (OS) or progression-free survival (PFS) associated with baseline levels of sPD-L1 in cancer patients undergoing immunotherapy treatment were considered eligible. Twelve studies involving 1076 patients and different tumor types treated with immunotherapy were included in the analysis. High blood levels of sPD-L1 correlated with poorer OS and PFS in cancer patients treated with immunotherapy (HR = 1.49, 95%CI: 1.15, 1.93, p < 0.01, I2 = 77% for OS; HR = 1.59, 95%CI: 1.20, 2.12, p < 0.01, I2 = 82% for PFS). A subgroup analysis highlighted that high levels of sPD-L1 were associated with worse survival in patients affected by NSCLC (HR = 1.81 95%CI: 1.09–3.00, p = 0.02, I2 = 83% for OS; HR = 2.18, 95%CI: 1.27–3.76, p < 0.01, I2 = 88% for PFS). An HR > 1 indicated that patients with low levels of sPD-L1 have the highest rates of OS/PFS. In this meta-analysis, we clarified the role of sPD-L1 in different solid cancers treated exclusively with Immune checkpoint inhibitors (ICIs). sPD-L1 could represent a non-invasive biomarker that is easily dosable in the blood of patients. The pooled data from the selected studies showed that a high circulating concentration of sPD-L1 in cancer patients correlates with worse survival, suggesting that it may be a helpful prognostic biomarker for the selection of cancer patients before immunotherapy, thus improving the efficacy of ICIs and avoiding unnecessary treatment.

Project description:Purpose: The clinical use of immunotherapies targeting programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) is rapid expanding, but the equivalency of these inhibitors remains unclear. We aimed to comprehensively compare the efficacy and safety of PD-1/PD-L1 inhibitors with a systematic review and Bayesian network meta-analysis Methods: We searched PubMed, Web of Knowledge, related reviews and abstracts for randomized controlled trials of five PD-1/PD-L1 inhibitors for patients with solid tumors before November 30th, 2018. We estimated summary hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for grade 3-5 treatment-related adverse events (TrAEs) using pairwise and network meta-analysis with random-effects. This study was registered with PROSPERO (#CRD42018116624). Results: Totally, 43 reports of 35 trials comprising 21261 patients were eligible for the analysis. Nivolumab, pembrolizumab, atezolizumab and durvalumab were more effective than control treatment, and no significant differences were identified in OS and PFS between any two inhibitors. Avelumab was associated with significantly inferior OS to nivolumab (HR 1.37, 95%CrI 1.05-1.78) and pembrolizumab (HR 1.33, 95%CrI 1.02-1.73), and with inferior PFS to nivolumab (HR 1.60, 95%CrI 1.03-2.51). Compared with placebo, nivolumab had increased risk of grade 3-5 TrAEs (OR 2.35, 95%CrI 1.35-4.17). Compared with standard-of-care, nivolumab (OR 0.39, 95%CrI 0.28-0.54), pembrolizumab (OR 0.43, 95%CrI 0.30-0.60), atezolizumab (OR 0.37, 95%CrI 0.21-0.64) and avelumab (OR 0.24, 95%CrI 0.12-0.48) significantly reduced grade 3-5 TrAEs. There were not significant differences in grade 3-5 TrAEs between any two inhibitors. Conclusion: This Bayesian network meta-analysis revealed that nivolumab, pembrolizumab, atezolizumab and durvalumab yielded equivalent survival, while avelumab was associated with unfavorable survival. PD-1/PD-L1 inhibitors were comparable in the risk of TrAEs, and safer than conventional therapies.

Project description:BackgroundAn increasing number of studies have examined the ability of programmed death-ligand 1 (PD-L1) to function as a marker for tumor prognosis. However, whether PD-L1 expression is a prognostic factor for the poor outcomes in many human cancers remains controversial. This study aims to investigate the prognostic role of PD-L1 expression through a meta-analysis update of 60 studies.MethodsThe studies were identified by searching PubMed, Embase, Google Scholar, and Cochrane Library, and were assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and stratified analyses were calculated to investigate the association between the PD-L1 expression and the overall (OS) and disease-free (DFS) or progression-free survivals (PFS) of cancer patients. Heterogeneity and publication bias were also investigated.ResultsThe results indicated that PD-L1 overexpression can predict a poor OS (HR = 1.58, 95% CI = 1.38-1.81, P <.000) and DFS/PFS (HR = 1.72, 95% CI = 1.26-2.33, P = .001). Subgroup analyses showed that PD-L1 overexpression was significantly related to the poor OS in patients with breast (HR = 1.98, 95% CI = 1.15-3.41, P = .014), urothelial (HR = 2.24, 95% CI = 1.61-3.12, P <.000), renal (HR = 3.30, 95% CI = 2.23-4.86, P <.000), and gastric cancers (HR = 1.56, 95% CI = 1.02-2.37, P = .040). Furthermore, PD-L1 overexpresion was significantly associated with poor DFS/PFS in patients with hepatocellular carcinoma (HCC) (HR = 1.72, 95% CI = 1.21-2.46, P = .003), melanoma (HR = 3.39, 95% CI = 2.02-5.69, P <.000), and renal carcinoma, (HR = 5.04, 95% CI = 2.87-8.86, P <.000). The adverse prognostic impact of PD-L1 was observed in patients of different ethnicities.ConclusionsThe findings of this meta-analysis suggest the correlation of PD-L1 overexpression with worse OS in patients with solid tumors. However, the correlations differed according to tumor types.

Project description:Background: Multiple anti-PD-1/PD-L1 antibodies have been approved, and in some diseases, there is a choice of more than one. Comparative efficacy, safety and tolerability are unknown. Methods: Randomized trials (RCTs) supporting the registration of single agent anti-PD1 or anti-PDL1 inhibitors between 2015-2019 were identified. We extracted the hazard ratio (HR) for overall survival (OS) and calculated the odds ratio (OR) for commonly reported safety and tolerability outcomes. We then performed a network meta-analysis, reporting multiple pair-wise comparisons between different anti-PD-1/PD-L1 antibodies. Results: Sixteen RCTs comprising 10673 patients were included; 10 in non-small-cell lung cancer, 2 in melanoma, 2 in head and neck squamous cell carcinoma and 2 in urothelial cancer. Compared to pembrolizumab, efficacy was similar for nivolumab (HR: 1.02 95% CI: 0.91-1.14) and for atezolizumab (HR: 0.97 95% CI: 0.85-1.10), however, avelumab appeared inferior (HR: 1.30, 95% CI: 1.06-1.56). Pembrolizumab showed similar odds of serious adverse events (SAEs) as nivolumab (OR: 1.12, 95% CI: 0.56-2.27) and atezolizumab (OR: 1.05, 95% CI: 0.55-2.04). Compared to nivolumab, atezolizumab was associated with more SAEs (OR: 2.14, 95% CI: 1.47-3.12). Avelumab had the lowest odds of grade 3-4 adverse events compared to pembrolizumab (OR: 0.42, 95% CI: 0.24-0.74), nivolumab (OR: 0.38, 95% CI: 0.24-0.62) and atezolizumab (OR: 0.21, 95% CI: 0.14-0.33). The odds of treatment discontinuation without progression were similar between nivolumab and atezolizumab (OR: 1.20, 95% CI: 0.73-2.00), and between pembrolizumab and nivolumab (OR: 1.35, 95% CI: 0.83-2.17), but was higher with atezolizumab compared to nivolumab (OR: 2.56, 95% CI: 1.29-5.00). Pembrolizumab was associated with higher OR of immune-related adverse events (IRAEs) compared to nivolumab (OR: 2.12, 95% CI: 1.49-3.03) and atezolizumab (OR: 1.63, 95% CI: 1.09-2.43). Conclusions: Pembrolizumab, nivolumab, and atezolizumab have similar efficacy. Avelumab appears less efficacious. Safety and tolerability seem better with avelumab, but worse with atezolizumab and pembrolizumab.

Project description:BackgroundThe effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors as neoadjuvant therapy for malignant solid tumors.MethodsThis study has been registered with the number CRD42023407275 on PROSPERO. Systematic searches were conducted in PubMed, Embase, Web of Science and Cochrane Library databases until March 17, 2023. In addition, manual searches were performed. The inclusion criteria encompassed randomized controlled trials (RCTs) that assessed the utilization of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors PD-1/PD-L1 inhibitors for patients with solid malignancies. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials (ROB1) were used. Risk ratios (RRs), hazared ratios (HRs) and their respective 95% confidence intervals were calculated using Stata17.0 MP and Review Manager 5.4 software.ResultsA total of 2780 records were identified, and ultimately 10 studies involving 273 patients were included. The meta-analysis showed that the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors did not demonstrate a significant effect on overall response rate, main pathological response, pathological complete response, surgical resection, radical resection, overall survival, progression-free survival, recurrence-free survival, grade 3-4 adverse events, all-cause mortality, and completed treatment (P > 0.05). However, further subgroup analysis indicated that the combination of PD-1 with CTLA-4 inhibitors significantly increased the occurrence of grade 3-4 adverse events in patients (P < 0.05).ConclusionsAs neoadjuvant therapy for malignant solid tumors, the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors does not appear to enhance efficacy.Moreover, there is a potential increase in the risk of grade 3-4 adverse events associated with this combination. However, it is important to note that the studies included in this analysis suffer from limitations such as small samples and single-center designs, which are inherent constrains with the available published literature. Further research involving large-sample and multicenter RCTs are warranted to obtain more reliable results.

Dataset Information

PD-L1 and Survival in Solid Tumors: A Meta-Analysis.

Background

Methods

Results

Conclusions

Publications

PD-L1 and Survival in Solid Tumors: A Meta-Analysis.

Similar Datasets

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