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

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.