Early efficacy results from atezolizumab (ATZ) with split doses of cisplatin plus gemcitabine in patients with locally advanced or metastatic urothelial carcinoma (SOGUGAUREA).

502 Background: Urothelial carcinoma (UC) commonly affects patients (pts) who are ineligible for full doses of cisplatin-based chemotherapy (CT) due to bad performance status, advanced age, or renal impairment. The combination of split-dose cisplatin with ATZ might be a feasible treatment for pts with UC who are unfit for full doses of cisplatin. Methods: The phase II SOGUG-AUREA clinical trial recruited treatment-naive pts in advanced or metastatic settings considered unfit for full dose of platinum-based CT. Pts received a split dose of cisplatin (35 mg/m2) and gemcitabine (1000 mg/m2) days 1 and 8 (up to 6 cycles) in combination with 3-weekly ATZ 1200 mg in D1 intravenously until progression, unacceptable toxicity, or absence of clinical benefit. Here we present the early results from the confirmed objective response rate (ORR) according to RECIST 1.1, the primary endpoint for efficacy, progression-free survival (PFS), overall survival (OS) and safety. Results: Between Jan 2021 and Mar 2022, 82 pts were screened, 66 pts were enrolled and received at least one dose of study treatment. Baseline characteristics are outlined in the table. The median duration of ATZ treatment was 4.4 months (m) (95%CI: 4.1-4.6). The confirmed ORR was 40.9%, with 5 (7.6%) pts having CR and 22 (33.3%) PR. The median duration of the response was 7 m (95%CI: 4.9-10.4). The clinical benefit rate (CBR) was 53%, and SD (maintained > 6m) was reported in 8 (12.1%) pts. Eight (12.1%) pts were not evaluable for response due to exitus previous to disease evaluation (9.1%), non measurable target lesions (1.5%) or withdrawal (1.5%). With a median follow-up of 9.3 m (range: 0.6-18.1), the median PFS was 6.9 m (95%CI: 6.4-9.2), with a 6-m PFS rate of 67.1% (95% CI: 56.5-79.7). The reasons for platinum ineligibility did not correlate with PFS. The 6-m OS rate was 78.2% (95%CI: 68.6-89). Most frequent grade 3-4 toxicities were neutrophil count decreased (24.2%), anemia (21.5%) and platelet count decreased (13.6%). Conclusions: ATZ with split doses of CT was safely administered in a population of frail pts with mUC who were unfit for CT showing promising preliminary survival outcomes in terms of response. Final survival results are awaited. Clinical trial information: NCT04602078 . [Table: see text]