Avelumab maintenance therapy: effective standard of drug therapy of metastatic urothelial carcinoma

Background. Maintenance therapy with avelumab is the standard of care for patients with metastatic and locally advanced inoperable urothelial carcinoma who have not progressed with platinum-based chemotherapy. Between 2021 and 2024, 40 patients with metastatic and locally advanced inoperable urothelial carcinoma were treated at the N. A. Lopatkin Research Institute of Urology and Interventional Radiology and the Moscow Center for Immunotargeted Therapy. Their disease was confirmed to be controlled after 4–6 courses of platinum-based chemotherapy followed by maintenance therapy with avelumab.

Aim. To evaluate the efficacy and tolerability of maintenance therapy with avelumab in metastatic urothelial cancer in real-world clinical practice.

Materials and methods. The study included 11 women (27.5 %) and 29 men (72.5 %), aged 39 to 80 years. Mean age was 63.95 ± 10.9 years, median age was 65.5 (interquartile range 58.3–72.0 years). Patients were divided by primary tumor location as follows: bladder cancer (24 patients; 60 %), upper urinary tract cancer (14; 35 %), and multiple primary cancer (combined lesions) (2; 5 %).

All patients received 4–6 cycles of platinum-based chemotherapy in the first line, with 28 (70 %) patients starting with the gemcitabine + cisplatin combination. Gemcitabine + cisplatin was used throughout treatment in 24 cases (60 %), gemcitabine + carboplatin (30.0 %) was used in 12 cases, and 4 (10 %) patients underwent a switch from gemcitabine + cisplatin to gemcitabine + carboplatin. Chemotherapy resulted in complete response in 6 patients (15 %), while the remaining patients experienced partial response (37.5 %) or stable disease (47.5 %). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method from the start of first-line chemotherapy. A subgroup analysis was performed to assess 12-, 24-, and 36-month PFS, taking into account prognostic factors.

Results. The median follow-up was 23.3 months (6 to 54, interquartile range 27.1–45.8 months). Median PFS from the start of chemotherapy was 18 months (95 % confidence interval (CI) not reached – 11 months). PFS at 12, 24, and 36 months was 63.2 % (95 % CI 45.9–76.3), 49.3 % (95 % CI 32.5–64.0), and 45.8 % (95 % CI 29.1–61.0), respectively. PFS from the start of avelumab therapy was 14 months. Median OS was not reached at the time of analysis (95 % CI not reached – 22 months). OS at 12, 24, and 36 months was 88.9 % (95 % CI 73.1–95.7), 58.3 % (95 % CI 39.5–73.0), and 54.4 % (95 % CI 35.6–69.8), respectively. Better PFS rates were demonstrated in patients with a complete response to platinum-based therapy compared with those with partial response or stable disease, in patients receiving cisplatin compared with carboplatin, in patients with lymph node-only metastases compared with other metastatic sites, and in primary bladder tumors compared with upper urinary tract cancer. Immune-related adverse events were reported in 50 % of patients, but only in 7.5 % (n = 3) of cases did these lead to avelumab discontinuation. Therapy interruption occurred in 1 patient.

Conclusion. Real-world clinical practice has demonstrated that maintenance therapy with avelumab is an effective strategy for long-term disease control in patients with metastatic and locally advanced inoperable urothelial cancer, with an acceptable immune-mediated toxicity profile.