Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes

Background: First-line therapy for treatment of advanced urothelial carcinoma includes combination platinum-based chemotherapies, though resistance and long-term toxicity concerns to these regimens cause limitations in progression-free survival and overall survival. Maintenance treatment with an alternative agent such as the PD-L1 inhibitor, avelumab (Bavencio (R)), after initial chemotherapy has been shown to prolong overall survival. The aim of this review is to provide a landscape clinical use of avelumab in the treatment of advanced urothelial carcinoma with a focus on patient selection and outcomes. Methods: This review includes the most up to date phases and results from clinical trials published in peer-reviewed journals. Results: Three studies were included, one phase 1B trial, one phase 1B trial with 2 year follow-up, and one phase 3 trial. Patients receiving avelumab maintenance therapy at 10 mg/kg IV every two weeks had an overall better performance status, though those with an increased ECOG-PS, increased Bellmunt risk score, or failure of >= 3 chemotherapies had poorer responses. Patients over the age of 65 had a higher ORR (18-25%) compared to younger patients (13-14%). Patients with PD-L1 positive tumors had a significantly increased CR median ORR (13.8%), median PFS (5.7 months), and median 12-month OS rate (79.1%) compared to control subjects receiving best supportive care (1.2%, 2.1 months, 60.4%, respectively). TRAEs were seen in 86.7% of patients, with 32.4% of patients experiencing a >= grade 3 AE. The most common AE was IRR (32.4%, >= grade 3 1.01%) and irAE 25.6% of any grade, including various rashes and pruritus AEs, immune-related thyroid disorders, and immune related hepatitis. There were 3 reported treatmentrelated deaths (0.05%). Ongoing phases of one of the trials is investigating the use of docetaxel and avelumab together after failure of one chemotherapy. Conclusion: Avelumab as a maintenance therapy after platinum-based chemotherapy failure or in platinum-ineligible patients with advanced or metastatic urothelial carcinoma is an effective option with increased ORR, PFS, and OS with a similar safety profile to other chemotherapies. Ongoing studies currently in recruitment and active clinical trials will yield valuable insights into optimizing avelumab therapy in conjunction with chemotherapies and/or immunotherapies, better characterization of response for PD-L1 positive tumors, and a clearer insight into clinically validated prognostic factors to improve patient outcomes.

Automated summary

Avelumab is an effective option as a maintenance therapy for advanced urothelial carcinoma after platinum-based chemotherapy failure or in platinum-ineligible patients, with increased overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). This review summarizes the clinical use of avelumab in treating advanced urothelial carcinoma, focusing on patient selection and outcomes. Ongoing studies will provide valuable insights into optimizing avelumab therapy in combination with chemotherapies and/or immunotherapies, better characterization of response for PD-L1 positive tumors, and clinically validated prognostic factors to improve patient outcomes.