Grant D Stewart1, Maria De Santis2, Bernard Escudier3, Thomas Powles4, Guru Sonpavde5. 1. Academic Urology Group, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. 2. Cancer Research Centre, University of Warwick, Coventry, UK. 3. Gustave Roussy, Villejuif, France. 4. Bart's Cancer Institute, London, UK. 5. Department of Medicine, Section of Hematology-Oncology, University of Alabama at Birmingham (UAB), Birmingham, AL, USA. Electronic address: gsonpavde@uabmc.edu.
Abstract
CONTEXT: Current therapy for renal cell carcinoma (RCC) generally consists of the sequential administration of single agent therapy. Given the advent of T-cell checkpoint inhibitors, the role of combinations including these agents is being intensely interrogated. OBJECTIVE: To evaluate ongoing trials of combinations including immunotherapy and sequencing of agents to treat RCC. EVIDENCE ACQUISITION: Recent data and ongoing trials were analyzed to evaluate the direction of research in this arena. EVIDENCE SYNTHESIS: The favorable therapeutic index of programmed cell death 1/programmed death-ligand 1 inhibitors enable combinations of these agents. Multiple ongoing phase 3 trials are evaluating the first-line therapy of RCC using a combination of programmed cell death 1/programmed death-ligand 1 inhibitors with vascular endothelial growth factor inhibitors or cytotoxic T-lymphocyte-associated protein 4 inhibitors. The role of sequencing using single agent sunitinib and avelumab will be evaluated in a randomized phase 2 trial. The role of vaccine therapy remains unproven. The role of predictive biomarkers to select appropriate therapy requires a greater focus, given the multitude of possible therapies. CONCLUSIONS: Therapy for RCC should be tailored based on both patient and tumor characteristics. Combination therapy and sequencing of single agents may both play roles and are currently undergoing clinical trial evaluation. PATIENT SUMMARY: Combinations of immunotherapy with angiogenesis inhibitors are undergoing vigorous clinical trial evaluations. Sequencing of immunotherapy and antiangiogenic therapy is also undergoing investigation. Clinical trial participation is critically important to develop new drugs and combinations, and biomarkers to select therapy.
CONTEXT: Current therapy for renal cell carcinoma (RCC) generally consists of the sequential administration of single agent therapy. Given the advent of T-cell checkpoint inhibitors, the role of combinations including these agents is being intensely interrogated. OBJECTIVE: To evaluate ongoing trials of combinations including immunotherapy and sequencing of agents to treat RCC. EVIDENCE ACQUISITION: Recent data and ongoing trials were analyzed to evaluate the direction of research in this arena. EVIDENCE SYNTHESIS: The favorable therapeutic index of programmed cell death 1/programmed death-ligand 1 inhibitors enable combinations of these agents. Multiple ongoing phase 3 trials are evaluating the first-line therapy of RCC using a combination of programmed cell death 1/programmed death-ligand 1 inhibitors with vascular endothelial growth factor inhibitors or cytotoxic T-lymphocyte-associated protein 4 inhibitors. The role of sequencing using single agent sunitinib and avelumab will be evaluated in a randomized phase 2 trial. The role of vaccine therapy remains unproven. The role of predictive biomarkers to select appropriate therapy requires a greater focus, given the multitude of possible therapies. CONCLUSIONS: Therapy for RCC should be tailored based on both patient and tumor characteristics. Combination therapy and sequencing of single agents may both play roles and are currently undergoing clinical trial evaluation. PATIENT SUMMARY: Combinations of immunotherapy with angiogenesis inhibitors are undergoing vigorous clinical trial evaluations. Sequencing of immunotherapy and antiangiogenic therapy is also undergoing investigation. Clinical trial participation is critically important to develop new drugs and combinations, and biomarkers to select therapy.
Authors: Nick Hornigold; Karen R Dunn; Rachel A Craven; Alexandre Zougman; Sebastian Trainor; Rebecca Shreeve; Joanne Brown; Helen Sewell; Michael Shires; Margaret Knowles; Tsutomu Fukuwatari; Eamonn R Maher; Julie Burns; Selina Bhattarai; Mini Menon; Alvis Brazma; Ghislaine Scelo; Lara Feulner; Yasser Riazalhosseini; Mark Lathrop; Adrian Harris; Peter J Selby; Rosamonde E Banks; Naveen S Vasudev Journal: Br J Cancer Date: 2020-05-11 Impact factor: 7.640