Cancer Management and Research (Feb 2022)
Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes
Abstract
Jennifer E Ten Eyck,1 Navkirat Kahlon,2 Sonia Masih,1 Danae M Hamouda,2 Firas G Petros1 1Department of Urology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USA; 2Department of Hematology Oncology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USACorrespondence: Firas G Petros, Department of Urology, The University of Toledo, College of Medicine and Life Sciences, 3000 Arlington Ave., Mail Stop 1091, Toledo, OH, 43614-2598, USA, Tel +1 419 383 3584, Fax +1 419 383 3785, Email [email protected]: 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®), 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 treatment-related 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.Keywords: avelumab, Bavencio®, metastatic, advanced, urothelial carcinoma, patient outcomes
