Immunotherapy-based combination strategies for advanced urothelial cancer: A long quest

Despite longer survival with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1), metastatic urothelial carcinoma remains lethal. There is an unmet need to further improve the efficacy of these agents. In their phase 2 trial, Zhang et al. evaluated the combination of pembrolizumab (a PD-1 inhibitor) plus acalabrutinib (a novel agent inhibiting an enzyme considered relevant to immunotherapy resistance) based on strong rationale but did not demonstrate clinical benefit compared with pembrolizumab alone. Future trials that examine such promising rational combinations may be able to evaluate selected patients based on validated biomarkers to optimize benefit in an endless pursuit of personalizing therapies.