Real world effectiveness of systemic treatment in patients (pts) with advanced upper tract urothelial carcinoma (UTUC) with histological variants.

722 Background: Upper tract urothelial carcinoma is a rare and heterogeneous disease that accounts for up to 5% of all urothelial neoplasms. Variant histology is an important prognostic factor in patients affected by bladder cancer and its presence is associated with adverse pathological features and worse survival outcomes. However, few data exists regarding the impact of histological variants in patients affected by UTUC treated with systemic therapy. Methods: PEMBROBLAD is a retrospective multicenter RW study conducted in 24 French GETUG centers. Eligible patients had advanced UC with mixed variants (UC-V) or pure non-UC (NUC). All patients received ICI as a second line treatment. We identified all patients with UTUC within the whole study cohort. The primary endpoint was overall response rate (ORR) in first-line setting; secondary endpoints included disease control rate (DCR) in first-line setting, overall response rate (ORR) in second-line setting, DCR in second-line setting and overall survival (OS). Results: Out of 139 patients (pts) in the PEMBROBLAD cohort, 32 had UTUC. Median age was 72 years (range 49-88), 69.6 % were male with ECOG PS 0/1 in 64.5% of cases. Mixed UC represented 75% (n=24) of UTUC with histological variants. The most common were squamous cell carcinoma (n=9, 37.5%), micropapillary (n=7, 29.2%), sarcomatoïd (n=3, 12.5%), neuroendocrine (n=1, 4.2%), nested (n=4, 16.7%) and adenocarcinoma (n=3, 37.5%). Non UC concerned 25% (n=8) of UTUC with histological variants, including 4 patients with squamous cell carcinoma (n=4, 50%). Fifteen pts (46.9%) was treated with Carboplatin based combination in first-line and 14 pts (43.75%) with Cisplatin based treatment. The ORR was 33.3% and DCR was 50.0%. All patients received immunotherapy in second-line setting. The ORR was 18.7% and DCR was 28.1%. Median overall survival from first-line treatment is 8.9 months (CI95%, 3.6-18.5). Serious TRAE occurred in 5 pts (16.1%). Discontinuation due to TRAEs occurred in 9.6% of pts. Thirteen pts (41.9%) had a third-line of treatment. Conclusions: Our results suggest efficacy of chemotherapy in first-line setting and ICI in pretreated advanced UC-V and NUC. No new safety concerns were identified. Survival data will be updated for the meeting.