Dr Sonpavde on the Implications of the NIAGARA Trial Regimen in Bladder Cancer

“In bladder cancer, the key study is NIAGARA, which is a phase 3 trial that looked at neoadjuvant gemcitabine and cisplatin plus or minus durvalumab, a PD-L1 inhibitor.”

Guru P. Sonpavde, MD, medical director, Genitourinary (GU) Oncology, assistant director, Clinical Research Unit, Christopher K. Glanz Chair for Bladder Cancer Research, AdventHealth Cancer Institute, discusses the implications of treatment with the phase 3 NIAGARA trial (NCT03732677) regimen in patients with cisplatin-eligible muscle-invasive bladder cancer (MIBC).

Notably, data from the randomized, open-label, multicenter, global NIAGARA trial were presented at the 2024 ESMO Congress.

In MIBC, a key treatment development stems from the NIAGARA trial, a study that evaluated the efficacy of neoadjuvant gemcitabine and cisplatin with or without durvalumab (Imfinzi), a PD-L1 inhibitor, Sonpavde begins. Notably, the experimental arm also incorporated durvalumab as an adjuvant therapy. This trial demonstrated significant improvements in both event-free survival and overall survival with the durvalumab regimen, he reports. These results are expected to be practice changing, with the potential to influence clinical management in the near future, according to Sonpavde.

The positive outcomes from NIAGARA may pave the way for investigations of similar chemoimmunotherapy regimens, such as gemcitabine/cisplatin plus pembrolizumab (Keytruda) or nivolumab (Opdivo), in bladder cancer, Sonpavde continues. The likelihood of positive outcomes from these trials appears high, given the promising NIAGARA results, he adds. However, the integration of checkpoint inhibitors into earlier treatment settings raises important questions about their role in subsequent lines of therapy, he explains.

A major challenge is treating patients who experience disease progression following prior immune checkpoint inhibition, Sonpavde expands. Lessons from renal cell carcinoma indicate that continuing immune checkpoint inhibitors alongside VEGF inhibitors after progression does not confer significant benefit, he shares, adding that this raises concerns about the utility of immediate reintroduction of checkpoint inhibitors after progression in bladder cancer. 

Future research must address whether a treatment gap of 3 to 6 months could restore the efficacy of checkpoint inhibitors after prior use, he says. Caution is warranted, as premature re-administration may yield limited benefit, although carefully timed reintroduction could potentially enhance outcomes, he emphasizes. Further investigation will clarify these strategies, Sonpavde concludes.