Organ-Specific Tumor Response to Pembrolizumab in Advanced Urothelial Carcinoma After Platinum-Based Chemotherapy

Abstract

Background To evaluate the organ-specific therapeutic effect of pembrolizumab after the failure of platinum-based chemotherapy for advanced urothelial carcinoma (UC). Materials and Methods Patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy and who had measurable disease were retrospectively analyzed. The objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to Response Evaluation Criteria in Solid Tumors, version 1.1. Results We analyzed 69 patients (male, n=51; median age, 71 years) with 226 metastases. The ORR was 23.2%. In total, 32, 31, 16, 14, 13 and 7 patients had measurable lung (OSSR 31.3%), lymph node (OSSR 29.0%), local recurrence (OSSR 12.5%), primary tumor organ (OSSR 7.1%), liver (OSSR 23.1%) and bone (OSSR 28.6%) disease, respectively. The median overall survival (OS) for pembrolizumab was 10.9 months (95% confidence interval, 5.9‑13.7 months). Regarding organ-specific OS, a Log rank test significant differences in OS were confirmed between patients with and without primary tumor organ disease (p=0.046) and liver metastasis (p<0.001). Conclusion Metastases and primary tumor organ disease showed different tumor responses to pembrolizumab. The most prominent tumor response was found in lung metastasis and the least response was found in primary organ sites. The mechanisms of these different responses were unclear and there does not appear to be a constant trend between tumor shrinkage and OS in tumor sites. Further studies are needed.

Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study

“…The appearance of ICIs has certainly improved the prognosis of ur/mUC; however, the response rate is insufficient [ 3 ]. Furthermore, the activity of ICIs may be affected depending on the different immunities of metastatic locations [ 4 , 5 ], and some small and limited reports have shown that the effect of ICIs differs depending on the metastatic organ [ 6 , 7 ]. These factors may complicate the determination of treatment efficacy and strategy.…”

“…This outcome is judged to be progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) or the immune-related RECIST (irRECIST), which are widely used to determine the effectiveness of treatments [ 8 , 9 ]. However, knowledge of real-world clinical outcomes of MR and the organ-specific objective response rate (ORR) to pembrolizumab in ur/mUC patients is lacking [ 6 , 10 ]. Here, we performed a retrospective, multicenter, collaborative study to compare the outcomes of response patterns in patients treated with pembrolizumab.…”

Clinical Outcomes of Mixed Response to Pembrolizumab in Advanced Urothelial Carcinoma After Platinum-based Chemotherapy

“…We recently reported the organ-specific tumor response to pembrolizumab in advanced UC; however, we did not evaluate the clinical association between the mixed response and the OS. In this report, we evaluated the organ-specific therapeutic effect of pembrolizumab, and found a significant difference in the OS between patients with and without primary tumor organ disease and liver metastasis (17). A closer look at each of the four cases in the mixed response group revealed that three had a primary tumor organ disease and one had liver metastases.…”

“…For each metastatic organ, including with the primary tumor, the best response was classified as: i) CR (disappearance or reduction to <10 mm in the short axis for all LN metastases), ii) PR (>30% reduction), iii) stable disease (SD) (neither CR, PR nor PD), and iv) PD (>20% growth) (15)(16)(17). In addition, a mixed response was judged to be positive when measurable disease in multiple organs showed differing responses (e.g., PD plus either CR or PR in the same patient).…”

Significant Improvement of Prognosis After the Advent of Immune Checkpoint Inhibitors in Patients with Advanced, Unresectable, or Metastatic Urothelial Carcinoma: A Propensity Score Matching and Inverse Probability of Treatment Weighting Analysis on Real-World Data

“…A previous report has demonstrated that lung metastatic lesions are most likely to respond to pembrolizumab, whereas primary organ lesions are least likely to respond. 18 Based on this evidence, a cytoreductive removal of primary organs in patients with aUC with well-controlled metastatic lesions may have a good overall response to pembrolizumab. The analysis of OS in key subgroups in the KEYNOTE-045 trial revealed that the benefit of pembrolizumab over chemotherapy was noted in patients without liver metastasis and in those who had tumor programmed cell death ligand 1 combined positive score of more than 1%.…”