Keytruda as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin containing chemotherapy and whose tumours express PD L1 with a combined positive score (CPS) ≥ 10.

Atezolizumab or pembrolizumab are alternatives for patients with PD-L1 biomarker-positive tumours who are not eligible for cisplatin-based combination ChT.

...the NCCN Panel recommends pembrolizumab, atezolizumab, nivolumab, durvalumab, avelumab, or erdafitinib as preferred second-line systemic therapy options after platinum-based therapy. Atezolizumab and pembrolizumab are also recommended as preferred first-line therapy options for patients who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression for locally advanced or metastatic disease.

Randomization was stratified by IC of platinum and PD-L1 combined positive score (CPS) (≥10 vs <10)….Baseline characteristics were generally well-balanced across arms. Median PFS for P + C, P, and C for total pts was 8.3 mo, 3.9 mo, and 7.1 mo, respectively; median OS was 17.0 mo, 15.6 mo, and 14.3 mo, respectively. ...ORR was 54.7% for P + C, 30.3% for P, and 44.9% for C.

...phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum based chemotherapy to receive pembrolizumab...The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005)...Pembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. 

...Overall response rate (ORR), assessed using the RECIST version 1.1`Progression free survival (PFS)`PD-L1 expression...

...Cohort A: CR rate of high risk NMIBC in the overall population and the PDL1 positive population. ...

...Assess adverse events`Positive Predictive Value between PD-L1 Expression and clinical complete response`Positive Predictive Value between TMB and clinical complete response`Metastasis Free Survival`Overall Survival (OS)`Bladder-Intact Overall Survival`Invasive Bladder Recurrence Free Survival`Recurrence Free Survival (RFS)...

...PFS per RECIST 1.1 was assessed by BICR in all participants who had PD-L1 positive tumors (combined positive score [CPS] ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016.`...

...Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants`Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%`Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%`Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants`Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%`Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%`Overall Survival (OS) in All Participants`Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%`Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%`Progression Free Survival Rate (PFS Rate) at Month 6 in All Participants`Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%`Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%`Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants`Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%`Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%`Overall Survival Rate (OS Rate) at Month 6 in All Participants`Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%`Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%`Overall Survival Rate (OS Rate) at Month 12 in All Participants`Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%`Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%`Programmed Cell Death Ligand 1 (PD-L1) Expression Status`Number of Participants Who Experienced At Least One Adverse Event (AE)`Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)...

...Six-month PFS rates among the subsets of subjects with PD-L1 positive and PD-L1 negative tumors treated with pembrolizumab versus placebo.`...

...Cohort A: CR rate of high risk NMIBC in the overall population and the PDL1 positive population. ...

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We analyzed the response patterns of 50 UC patients who were treated with pembrolizumab...In this study, younger age, lower preoperative neutrophil-to-lymphocyte ratio (NLR), and positive PD-L1 expression were significantly correlated with longer progression-free survival and overall survival. Moreover, lower NLR and positive PD-L1 expression were independently associated with longer OS in multivariate analysis.

This exploratory multivariate analysis identified numerous factors, including PD-L1–positive status (CPS =10), lymph node only metastasis, and lower ECOG PS score, associated with improved clinical outcomes in pts with advanced UC treated with first-line pembro monotherapy.

PD-L1 expression in tumor cells was associated with poor prognosis (OS and PFS) and low DCR. Interestingly, the strong expression of Nectin-4 was correlated with high DCR. PD-L1 and Nectin-4 expression in tumor cells could be prognostic biomarkers useful for pembrolizumab in patients with advanced UC.

...374 patients were enrolled and 370 patients received at least one dose of pembrolizumab. 89 (24%, 95% CI 20-29) of 370 patients had a centrally assessed objective response, and as of Sept 1, 2016 (data cutoff), 74 (83%) of 89 responses were ongoing. Median follow-up was 5 months (IQR 3·0-8·6). A PD-L1-expression cutoff of 10% was associated with a higher frequency of response to pembrolizumab; 42 (38%, 95% CI 29-48) of 110 patients with a combined positive score of 10% or more had a centrally assessed objective response.

Here, we present a novel case report of the first Imaging Mass Cytometry (IMC) analysis done in SUC to investigate the immune cell repertoire and PD-L1 expression in a patient who presented with metastatic SUC and experienced a prolonged response to the anti-PD1 immune checkpoint inhibitor pembrolizumab after progression on first-line chemotherapy.