Dataset Information

Expression of PD-L1 for predicting response to immune checkpoint inhibitors in metastatic urothelial carcinoma: a systematic review and meta-analysis.

ABSTRACT:

Background

We conducted this meta-analysis and systematic literature review to study the ability of PD-L1 to predict objective response in patients with urothelial cancer treated with PD-1/PD-L1 inhibitors.

Methods

Relevant studies of PD-1 or PD-L1 inhibitors in urothelial cancer that reported objective response rate (orr) based on PD-L1 expression status in PubMed, embase, and the Cochrane Library were retrieved. Efficacy of PD-L1 expression status in predicting orr and the efficacy, safety of PD-1 and PD-L1 drugs were analyzed.

Results

Studies were divided into ?1%, ?5%, and ?25% based on PD-L1 positivity threshold, and the patients were grouped into PD-L1 positive and negative. In all 3 expression thresholds, patients with positive PD-L1 expression were more likely to experience an objective response [?1% threshold odds ratio (or): 1.74; 95% confidence interval (ci): 1.20 to 2.53; ?5% threshold or: 2.74; 95% ci: 2.01 to 3.724; ?25% threshold or: 7.13; 95% ci: 2.38 to 21.40] in comparison with patients with negative PD-L1 expression. Of the 3 thresholds, the ?25% threshold was better in predicting orr (1.74 vs. 2.93 vs. 7.13; p < 0.0001). The ?1% PD-L1 threshold had a relatively high sensitivity in predicting orr; the ?5% PD-L1 threshold was better for specificity. Sensitivity was higher at the ?25% threshold than at the other two thresholds, but specificity was lower. Further, we found that there is no statistically significant difference in efficacy between PD-1 and PD-L1 drugs.

Conclusions

Urothelial cancer patients with PD-L1 positive expression responded better than PD-L1 negative patients did, and a threshold of ?5% or greater for PD-L1 expression might predict positive clinical response.

SUBMITTER: Huang J

PROVIDER: S-EPMC7755433 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression of PD-L1 for predicting response to immune checkpoint inhibitors in metastatic urothelial carcinoma: a systematic review and meta-analysis.

Huang J J Teng X X

Current oncology (Toronto, Ont.) 20201201 6

<h4>Background</h4>We conducted this meta-analysis and systematic literature review to study the ability of PD-L1 to predict objective response in patients with urothelial cancer treated with PD-1/PD-L1 inhibitors.<h4>Methods</h4>Relevant studies of PD-1 or PD-L1 inhibitors in urothelial cancer that reported objective response rate (orr) based on PD-L1 expression status in PubMed, embase, and the Cochrane Library were retrieved. Efficacy of PD-L1 expression status in predicting orr and the effic ...[more]

PMID: 33380881

Similar Datasets

Project description:Most patients with advanced or metastatic urothelial carcinoma do not benefit significantly from Immune checkpoint inhibitors (ICIs) use. A systematic review and meta-analysis of randomized controlled trials to assess the efficacy and activity of ICIs, in terms of Overall Survival (OS), Progression-free survival (PFS), and Objective Response Rate (ORR). We systematically searched for articles from PubMed, Cochrane Library, Embase, and Web of science from their inception to December 1, 2020 with no language restrictions. The search was performed to identify all clinical trials (phase I, phase II, phase III) of ICIs for treating urothelial carcinoma. The endpoints of the meta-analysis were OS, PFS, and ORR, compared unselected patients and in the subgroup of patients characterized by high expression of PD-L1 (PD-L1 selected patients). Sixteen studies comprising 5559 patients were identified, of which data for OS comparison were available from 4 RCTs (2342 patients), two studies for PFS (649 patients), and four RCTs were eligible for ORR analysis (2921 patients). Both pembrolizumab and atezolizumab have showed to improve OS compared to chemotherapy in unselected patients (HR 0.86, 95% CI 0.80-0.93, P = .0001, I2 = 60%), while the difference was not significant in PD-L1 selected patients (HR 0.91, 95% CI 0.77-1.07, P = .23, I2 = 0%). PFS difference was not observed in neither unselected population nor PD-L1 selected patients, the pooled HR of PFS for immunotherapy compared to control treatment was 1.05 (95% CI 0.74-1.49, P = .79, I2 = 85%) and 0.84 (95% CI 0.68-1.03, P = .09, I2 = 0%, respectively. Similar result was observed in ORR, the pooled HR of ORR for immunotherapy compared to control treatment was 1.45 (95% CI 0.53-3.98, P = .47, I2 = 95%) and 2.19 (95% CI 0.79-6.08, P = .13, I2 = 83%), respectively. Immunotherapy could significantly improve survival advantage in unselected patients but not in PD-L1 selected population, indicating that PD-L1 expression may not be a reliable marker in previously platinum-treated patients.

Project description:BACKGROUND:PD-L1 immunohistochemistry (IHC) has been traditionally used for predicting clinical responses to immune checkpoint inhibitors (ICIs). However, there are at least 4 different assays and antibodies used for PD-L1 IHC, each developed with a different ICI. We set to test if next generation RNA sequencing (RNA-seq) is a robust method to determine PD-L1 mRNA expression levels and furthermore, efficacy of predicting response to ICIs as compared to routinely used, standardized IHC procedures. METHODS:A total of 209 cancer patients treated on-label by FDA-approved ICIs, with evaluable responses were assessed for PD-L1 expression by RNA-seq and IHC, based on tumor proportion score (TPS) and immune cell staining (ICS). A subset of serially diluted cases was evaluated for RNA-seq assay performance across a broad range of PD-L1 expression levels. RESULTS:Assessment of PD-L1 mRNA levels by RNA-seq demonstrated robust linearity across high and low expression ranges. PD-L1 mRNA levels assessed by RNA-seq and IHC (TPS and ICS) were highly correlated (p?<?2e-16). Sub-analyses showed sustained correlation when IHC results were classified as high or low by clinically accepted cut-offs (p?<?0.01), and results did not differ by tumor type or anti-PD-L1 antibody used. Overall, a combined positive PD-L1 result (?1% IHC TPS and high PD-L1 expression by RNA-Seq) was associated with a 2-to-5-fold higher overall response rate (ORR) compared to a double negative result. Standard assessments of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) showed that a PD-L1 positive assessment for melanoma samples by RNA-seq had the lowest sensitivity (25%) but the highest PPV (72.7%). Among the three tumor types analyzed in this study, the only non-overlapping confidence interval for predicting response was for "RNA-seq low vs high" in melanoma. CONCLUSIONS:Measurement of PD-L1 mRNA expression by RNA-seq is comparable to PD-L1 expression by IHC both analytically and clinically in predicting ICI response. RNA-seq has the added advantages of being amenable to standardization and avoidance of interpretation bias. PD-L1 by RNA-seq needs to be validated in future prospective ICI clinical studies across multiple histologies.

Dataset Information

Expression of PD-L1 for predicting response to immune checkpoint inhibitors in metastatic urothelial carcinoma: a systematic review and meta-analysis.

Background

Methods

Results

Conclusions

Publications

Expression of PD-L1 for predicting response to immune checkpoint inhibitors in metastatic urothelial carcinoma: a systematic review and meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets