Two novel agents have the potential to transform the treatment landscape for urothelial carcinoma (UC), according to a review published in the British Journal of Cancer.

The review, by a group of UK-based authors led by Professor Robert Jones, medical oncologist at the Beatson West of Scotland Cancer Centre, highlighted that UC treatment outcomes remain poor overall but that new agents on the horizon could broaden and improve management of advanced disease.

While platinum-based chemotherapy remains the cornerstone of systemic treatment for patients with UC, the landscape is rapidly changing with several potential new therapies, they said.

Sacituzumab govitecan, an antibody-drug conjugate (ADC) that targets trophoblast cell-surface antigen 2, has shown promising results in patients with advanced UC, specifically those who had disease progression in spite of platinum-based chemotherapy and immune checkpoint inhibitor (ICI) therapy.

According to the review authors, results of ongoing Phase III trials suggest that sacituzumab govitecan could be an option for patients who are not benefitting from conventional treatment strategies.

Likewise, erdafitinib, a small-molecule fibroblast growth factor receptor (FGFR) inhibitor, has shown an improved five-year overall survival rate compared to conventional chemotherapy in patients with UC who have previously received treatment including ICIs.

Both drugs have received regulatory approval in the US as treatments for metastatic or advanced UC, but are yet to be approved in Europe or in the UK.

In the meantime, the authors stressed the importance of patients receiving optimal treatment at each decision point in the care pathway, while awaiting more evidence on the novel agents as well as consensus on key areas of uncertainty, particularly regarding the optimal number of first-line chemotherapy cycles for advanced UC, and the value of PD-L1 testing.

In summary, the current standard of care at each point in the bladder cancer treatment pathway should be as follows, the authors suggest:

• Neoadjuvant cisplatin-based chemotherapy for eligible patients with muscle-invasive bladder cancer, which is preferable to adjuvant treatment;
• Cisplatin- or carboplatin-based chemotherapy for first-line treatment of advanced UC (in patients eligible for platinum-based therapy), followed by avelumab maintenance in those who do not experience disease progression;
• Immune checkpoint inhibitors are recommended as an option for patients with programmed death ligand 1 (PD-L1)-positive tumours who can’t take platinum-based chemotherapy; and
• With regard to second-line or later treatment options, the optimal choice will depend on patient’s prior therapy; for example, enfortumab vedotin should be the go-to choice after previous ICI and chemotherapy, while other options include treatment rechallenge.