Avelumab maintenance therapy for metastatic urothelial carcinoma: Efficacy analysis and sequential therapies from a multicentric oncology network.

e16571 Background: Metastatic urothelial cancer (MUC) is a challenging condition with high mortality rates and generally poor prognosis. Avelumab is an immunotherapy recently approved as maintenance therapy following chemotherapy, based on the Javelin100 trial (Powles et al.), but its use has been challenged by new first-line combinations (Enfortumab/Pembrolizumab). Real-world-data is crucial to understand patterns of sequential therapies after avelumab progression as well as to validate its activity as many patients may not be able to receive several lines of therapy. Methods: This retrospective study analyzed a cohort of patients who received avelumab treatment from 2021 to 2024 across multiple oncology centers in Brazil. The primary endpoint of the study was to evaluate efficacy through progression-free survival (PFS), while secondary endpoints comprised overall survival (OS), toxicity, and identification of subsequent therapies following avelumab progression. Results: Out of 53 patients, 6 were excluded due to loss of follow-up or incomplete records, leaving 47 patients for analysis with a median follow-up of 13.7 months (range 0.2–40.6). The median age was 71 years old (55–91), and 31 (63.8%) were male. Regarding primary tumor location, 33 (70.2%) had bladder cancer, and 14 (29.8%) had upper urothelial tract cancer. In terms of metastasis, 33 (70.2%) had lymph node involvement, 21 (44.7%) had visceral metastases, and 11 (23.4%) had bone metastases. Prior platin-chemotherapy was administered to all patients with median of 4 cycles (3–7), 22 (46.8%) receiving carboplatin + gemcitabine, 21 (44.7%) receiving cisplatin + gemcitabine, and 4 (8.5%) receiving DD-MVAC. A median 11 cycles of avelumab (1–87) were given. PD-L1 status was positive in 5 out of 13 patients tested, and FGFR mutations were observed in 12,8% of patients. The median PFS was 11.2 months (1.8 - 40.6), and the median OS was 20.2 months (4.7 - 76.4). Grade 3/4 toxicities were reported in 10,6% of patients. After avelumab progression, 19 patients (40.4%) received second-line therapy, and 5 (10.6%) received third-line therapy. Second-line therapies consisted of: enfortumab vedotin (EV) 57.9%, erdafitinib 15.8%, pembrolizumab 10.5%, chemotherapy 10.5% and EV + pembrolizumab in 5.3%. In third-line therapy, 40% received chemotherapy, 20% received EV + pembrolizumab, 20% erdafitinib and 20% received pembrolizumab. Conclusions: Our resultsconfirmed avelumab benefit in patients with MUC, with a median PFS and OS after avelumab compared to phase 3 trials. A smaller fraction of patients received sequential therapies. These findings highlight the need for effective first-line therapies to avoid early disease progression.