Introduction: According to the KEYNOTE-045 Phase III trial, pembrolizumab is approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) that progressed after the first-line with platinum-based chemotherapy with benefit in OS, PFS and ORR, regardless of PD-L1 expression. However, in clinical practice, pembrolizumab is effective in a limited number of patients with mUC and the role of PD-L1 expression in second-line therapy is uncertain. Therefore, the development of clinical biomarkers with prognostic value is essential to personalize the choice of treatments and improve outcomes.
Objective: The aim of this retrospective study is to evaluate the prognostic and predictive value of neutrophil/lymphocyte ratio (NLR) and PD-L1 expression as clinical biomarkers in the patients with metastatic urothelial carcinoma treated with pembrolizumab in second-line.
Methods: We analyzed retrospectively 16 patients with metastatic urothelial carcinoma refractory to platinum-based chemotherapy who received second-line pembrolizumab between December 2017 and March 2021. Pretreatment NLR was calculated by dividing the number of neutrophils by the number of lymphocytes in peripheral blood, before the first administration of pembrolizumab and the PD-L1 expression was evaluated in the tumor specimen (CPS). Progression-free survival (PFS) and overall survival (OS) were compared by the Kaplan-Meier method and the Cox proportional hazard model.
Results: Overall 80% are male, with a median age of 70 (range: 55-82) years. Patients with NLR ≤ 5 before starting treatment with pembrolizumab had a median PFS of 13 months (7.71-14.57) and those with NLR > 5 was 8 months (4.07-10.35 ) (p < 0.001). In the multivariate analysis, the presence of bone metastases (HR: 3.01, 95% CI: 1.73-5.61, p = 0.021) and NLR> 5 (HR: 2.97, 95% CI: 2, 69-9.02, p<0.001) were independent predictors for shorter PFS and lower ORR. When the same analysis was performed for OS, it was not statistically significant, however, NLR ≤ 5 pretreatment with pembrolizumab and PD-L1 CPS > 10 were associated with better OS (p < 0.027) and ORR (p < 0.001).
Conclusion: These data suggest that pretreatment NLR can estimate the ORR, PFS and OS of patients with mUC treated with second-line pembrolizumab and that NLR ≤ 5 is a potential biomarker predicting response to second-line pembrolizumab as well as PD -L1 CPS > 10 and it may represent accessible tools in clinical practice to identify appropriate patients for second-line treatment with pembrolizumab. Prospective studies and clinical trials are needed to validate NLR as predictive biomarker of response to checkpoint inhibitors in mUC.

Prognostic value of Pretreatment Neutrophil-to-lymphocyte ratio and status PD-L1 for pembrolizumab in second-line in metastatic Urothelial Carcinoma in a portuguese Center – Real World Data

For 2021, our focus remains: turning new data into your daily practice. The programme will consist of state-of-the-art lectures, case discussions and panel debates. Our faculty is a group of international & multidisciplinary experts.

We will take you on our journey to Ghent and beyond. Prior the congress, we send out case challenges, where you can compare your opinion with peers & experts. These cases will be part of the Global Congresses on Prostate & Bladder Cancer programme during the congress days (12 & 13 October for PROSCA and 14 & 15 October for BLADDR). After these days, you will be updated on prostate & bladder cancer management.