Site and number of metastases predict outcomes in avelumab maintenance for advanced UC: results from meet-URO 25.

BACKGROUND

In advanced urothelial carcinoma (UC), the prognostic impact of metastatic site and burden during avelumab maintenance therapy remains poorly defined.

METHODS

We performed a sub-analysis of the Italian multicenter retrospective-prospective observational study Meet-URO 25, including patients with advanced UC who received avelumab maintenance after disease control with first-line platinum-based chemotherapy. We assessed the association between metastatic site and number of metastatic sites at the start of avelumab and clinical outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

RESULTS

A total of 243 patients were included. Lymph nodes (79.0%), lungs (32.1%), and bones (27.2%) were the most common metastatic sites. The median number of metastatic sites at the start of avelumab maintenance was 1. ORR and disease control rate (DCR) were higher in patients with nodal-only disease (ORR 28.9%, DCR 69.4%) and significantly lower in those with bone metastases (ORR 9.8%, DCR 50.8%). Median PFS and OS were 7.4 and 24.1 months, respectively, in the overall cohort. Bone metastases were associated with markedly shorter PFS (3.7 vs. 8.2 months; HR 1.92, p < 0.001) and OS (11.3 vs. 27.6 months; HR 2.44, p < 0.001), especially when present as a single metastatic site. Increasing number of metastatic sites was also associated with poorer outcomes (OS: 35.5 months with one site vs. 11.9 months with ≥ 3 sites; p < 0.001).

CONCLUSIONS

In this real-world cohort, both metastatic site and burden strongly influenced response and survival of avelumab. Bone metastases were independently associated with poor prognosis, while nodal-only disease identified a favorable subgroup. These findings support risk-based treatment stratification in the maintenance setting.