Difference of oncological efficacy between two immune checkpoint inhibitors following first-line platinum-based chemotherapy in patients with unresectable, metastatic, advanced urothelial carcinoma: a multicenter real-world Japanese cohort.

BACKGROUND: Maintenance avelumab is currently recommended for patients with unresectable and/or metastatic (mUC) achieving at least stable disease (SD) on first-line platinum-based chemotherapy (1L-CT). Pembrolizumab is an alternative therapeutic avenue for this patient cohort in clinical practice. We investigated real-world data, focusing on the correlation between response to 1L-CT and oncological efficacy of subsequent immune checkpoint inhibitor (ICI) therapy with avelumab or pembrolizumab. METHODS: A multicenter database registered 626 patients with mUC diagnosed from 2008-2023; among these, 175 receiving 2-6 cycles of 1L-CT followed by ICI therapy. Patients were categorized based on response to 1L-CT using the Response Evaluation Criteria in Solid Tumors (v1.1). Objective response rate on ICI, progression to ICI-free survival (ICI-PFS), and overall survival from start of 1L-CT were compared between avelumab-treated and pembrolizumab-treated patients in each response subgroup. RESULTS: ICI-PFS was significantly longer in patients achieving partial response on 1L-CT and subsequently receiving pembrolizumab compared to those receiving avelumab. Notably, patients achieving SD on 1L-CT and subsequently receiving pembrolizumab manifested significantly higher objective response rate (14% and 41%, respectively) and prolonged ICI-PFS relative to those receiving avelumab. In contrast, overall survival did not delineate difference between patients treated with avelumab versus pembrolizumab. Similar findings were discerned in the subanalysis of patients having favorable SD (tumor shrinkage, from - 29 to 0%) and unfavorable SD (tumor enlargement, from + 1 to + 19%) on 1L-CT. CONCLUSIONS: Our study provides real-world evidence regarding difference of oncological efficacy between maintenance avelumab and subsequent pembrolizumab in patients with mUC who achieved partial response or SD on 1L-CT.

Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort.

OBJECTIVE: Real-world evidence regarding enfortumab vedotin for unresectable or metastatic urothelial carcinoma is scarce, particularly in Japan. We investigated real-world data focusing on patient background, previous treatments, response, survival and adverse events in patients receiving enfortumab vedotin. METHODS: A multicentre database was used to register 556 patients diagnosed with metastatic urothelial carcinoma from 2008 to 2023; 34 patients (6.1%) treated with enfortumab vedotin were included. Best radiographic objective responses were evaluated using the Response Evaluation Criteria in Solid Tumors (v1.1) during treatments. Overall survival and progression-free survival were estimated (Kaplan-Meier method). Toxicities were reported according to the Common Terminology Criteria for Adverse Events, version 5.0. The relative dose intensity, which could impact oncological outcomes, was calculated. RESULTS: The median number of enfortumab vedotin therapy cycles was 5. The best objective response to enfortumab vedotin was partial response, stable disease and progressive disease in 19 (56%), 5 (15%) and 10 (29%) patients, respectively. The median overall survival and progression-free survival after the first enfortumab vedotin dose were 16 and 9 months, respectively. No significant relationship was observed between survival outcomes after enfortumab vedotin initiation and the enfortumab vedotin relative dose intensity. The median overall survival from first-line platinum-based chemotherapy initiation was 42 months. Twenty-six (76%) patients experienced any grade of enfortumab vedotin-related toxicities; eight (24%) experienced Grades 3-4 toxicities, the most common being skin toxicity (any grade, 47%; Grades 3-4, 12%). CONCLUSIONS: Here, we report real-world evidence for enfortumab vedotin therapy in Japan. Tumour responses and safety profiles were comparable with those of clinical trials on this novel treatment.

First-line pembrolizumab for patients with early relapsing urothelial carcinoma after perioperative chemotherapy: a retrospective analysis of bladder cancer and upper urinary tract cancer.

BACKGROUND: First-line pembrolizumab is available for recurrent disease within 12 months after the receipt of platinum-based perioperative chemotherapy. However, the benefit of first-line pembrolizumab is unclear. This study evaluated the oncological outcome of patients treated with pembrolizumab compared with chemotherapy as first-line therapy for early relapsing disease after the receipt of platinum-based perioperative chemotherapy. METHODS: Data from a multicenter study included 454 patients diagnosed with unresectable or metastatic UC from November 2006 to July 2021. We identified patients with early and non-early relapsing disease. Oncological outcomes were evaluated using progression-free survival, overall survival, and survival with disease control. RESULTS: Fifty-three patients with early relapsing disease and 15 patients with non-early relapsing disease were identified. Of 53 patients with early relapsing disease, 26 (49.1%) were treated with pembrolizumab and 27 (50.9%) were treated with chemotherapy as first-line therapy. Fifteen patients with non-early relapsing disease were treated with chemotherapy. Early relapsing disease was associated with shorter progression-free survival and overall survival than non-early relapsing disease. Pembrolizumab was associated with longer progression-free survival and survival with disease control than chemotherapy in patients with early relapsing disease. There was no significant difference in overall survival between pembrolizumab and chemotherapy, but overall survival plateau with a long tail was observed in pembrolizumab. CONCLUSIONS: First-line pembrolizumab in earlier clinical settings for highly malignant tumors might improve the prognosis of patients with early relapsing disease after the receipt of platinum-based perioperative chemotherapy.