This review explores the current landscape of treatments which target the DNA damage response (DDR) in metastatic and muscle-invasive bladder cancer. It emphasizes recent clinical trials which integrate DDR inhibitors with standard chemotherapy and immunotherapy.
Noteworthy findings include the ATLANTIS trial, which demonstrated prolonged progression-free survival (PFS) in DDR biomarker-selected patients using PARP inhibitors as maintenance after standard chemotherapy. Trials such as BAYOU, which combined immunotherapy with PARP inhibition, similarly suggested a potential therapeutic benefit in DDR biomarker-selected patients with bladder cancer. Efforts to develop bladder-sparing treatment regimens based on DDR-associated mutational profiles, such as the RETAIN and HCRN 16-257 trials, have had mixed outcomes to date. There are now ongoing efforts to combine DDR inhibitors with the newest bladder cancer therapies, such as antibody-drug conjugates. This review highlights the most recent advances in targeting DNA repair deficiency in the evolving treatment landscape of bladder cancer.
Current urology reports. 2024 Oct 09*** epublish ***
Vincent D D'Andrea, Christopher J Magnani, John Ernandez, Joaquim Bellmunt, Matthew Mossanen, Timothy N Clinton, Filipe L F Carvalho, Kent W Mouw
Brigham & Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. ., Brigham & Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.