- The treatment of urothelial carcinoma is in a transitional phase, moving away from “pure” chemotherapy to also utilising immune-oncology, targeted drugs, or combinations of these.
Why this matters
- This indication lags behind others in the application of new drugs, such as immune checkpoint inhibitors and targeted therapies.
- A consensus molecular classification of muscle-invasive bladder cancer has been proposed from 1750 transcriptomic profiles. Based on 7 key genes, these classes are: luminal papillary (24%), luminal nonspecified (8%), luminal unstable (15%), stroma-rich (15%), basal/squamous (35%), and neuroendocrine-like (3%). This should facilitate testing and validation of predictive biomarkers in future prospective clinical trials.
- Sacituzumab, enfortumab, and erdafitinib (for FGFR-selected patients) are novel agents in development that showed overall response rates of 31%, 43%, and 40% in patients with at least 1 line prior chemotherapy. Overall survival was 16.3 months, 12.3 months, and 13.8 months respectively.
- There are numerous potentially synergistic combinations of immune-oncology, chemotherapy, targeted therapy, and other approaches. IMVigor130, DANUB, KEYNOTE-361, Checkmate-901, and NILE study are all ongoing phase 3 studies with a total of almost 5000 patients.
- Combining chemotherapy with immunotherapy may better control rapid progression, but chemotherapy is also immunosuppressive and may promote tolerance. For sequencing strategies, there is even more uncertainty.