Effectiveness of anti-PD-1/PD-L1 antibodies in urothelial carcinoma patients with different PD-L1 expression levels: a meta-analysis

// Junqi Liu 1, * , Chuanfeng Zhang 1, * , Jiegang Hu 1 , Qing Tian 1 , Xin Wang 1 , Hao Gu 1 , Song Zhang 1 , Di Zhao 2 and Ruitai Fan 1 1 Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, 450000 Zhengzhou, Henan, China 2 Endocrinology Department, The First Affiliated Hospital of Zhengzhou University, 450000 Zhengzhou, Henan, China * These authors contributed equally to this work Correspondence to: Ruitai Fan, email: fanruitai@126.com Keywords: programmed death-1 (PD-1); programmed death-ligand 1 (PD-L1); urothelial carcinoma; meta-analysis Received: September 18, 2017      Accepted: December 05, 2017      Published: January 13, 2018 ABSTRACT Background: Urothelial carcinoma ranks the ninth among malignant cancers. We conducted this study to identify which patients could benefit more from the treatment of programmed death-1 (PD–1)/programmed death-ligand1 (PD–L1) inhibitors. Materials and Methods: We performed literature searches, combined data from qualified literature and performed comparative analyses on the effectiveness of anti-PD–1/PD–L1 antibodies in patients with different PD–L1 expression levels. Results: We divided patients into three groups according to the percentages of PD–L1-positive cells, namely the low- PD-L1 (PD-L1 < 1%), the medium-PD-L1 (PD-L1 ≥ 1 and < 5%) and the high–PD–L1 (PD-L1 ≥ 5%) groups. We found that the high-PD-L1 group responded significantly better than other groups ( P = 0.0003, ORs = 0.45, 95%CI: 0.29-071; P = 0.0009, ORs = 0.43, 95%CI: 0.25-0.73, for low-PD-L1 and medium-PD-L1 groups, respectively), while the latter two groups responded similarly ( P = 0.90, ORs = 1.06, 95%CI: 0.62-1.83) to both PD–1 and PD–L1 inhibitors. Furthermore, we found that the medium-PD–L1 and high-PD–L1 groups responded similarly to PD-1/ PD-L1 inhibitors ( P = 0.65, ORs = 1.11, 95%CI: 0.69–1.77), while the low-PD–L1 group responded better to PD-1 inhibitors than PD-L1 inhibitors ( P = 0.046, ORs = 1.92, 95%CI: 0.98–3.89). Conclusions: Our results suggest that PD–L1 positive patients should be defined as those with ≥ 5% or greaterPD-L1-positive cells. PD-1 antibodies performed better only in the low-group patients, likely because they could block the interactions of PD–1 with both PD–L1 and PD–L2.