Affiliation:
1. Department of Hematology and Oncology, Cleveland Clinic, Cleveland, OH, USA
Abstract
INTRODUCTION: While switch maintenance therapy is being increasingly investigated in solid tumors, it is a standard in only a few. We conducted a systematic review on switch maintenance therapy for metastatic urothelial carcinoma. EVIDENCE ACQUISITION: In this systematic review, we conducted a literature search in PubMed and Cochrane databases up to 2021, based on PRISMA statement guidelines. One hundred and fifty eight articles were identified and after a three-step selection process and six articles, using different agents were included in evidence synthesis. The primary end points were effect on overall survival, progression free survival, safety and tolerability. EVIDENCE SYNTHESIS: In the pre-immunotherapy era, targeted therapies like sunitinib, lapatinib and vinflunine were studied as switch maintenance therapy in metastatic urothelial carcinoma but did not show any overall survival benefit. Use of anti-PD-1/PD-L1 agents have shown promise as switch maintenance therapy; pembrolizumab showed improvement in progression free survival in a phase 2 trial and avelumab showed improvement in overall survival and progression free survival in the phase 3 JAVELIN Bladder 100 trial. CONCLUSION: Immunotherapy with anti-PD-1/PD-L1 agents has emerged as an effective switch maintenance strategy in patients with metastatic urothelial carcinoma. Intensification of the immunotherapy backbone in this setting can potentially further enhance outcomes. Emerging evidence shows a potential role of Poly (ADP-ribose) polymerase (PARP) inhibitors in this setting as well. Results from ongoing and planned studies will help us understand which switch maintenance approaches would be most effective for improving outcomes in metastatic urothelial carcinoma.