Durvalumab/Chemotherapy Deserving of Consideration in Neoadjuvant MIBC

Guru P. Sonpavde, MD, medical director of Genitourinary Oncology, assistant director of the Clinical Research Unit, and Christopher K. Glanz Chair for Bladder Cancer Research at the AdventHealth Cancer Institute, spoke with CancerNetwork® about additional results presented at the 2025 ASCO Genitourinary Cancer Symposium from the “landmark”, phase 3 NIAGARA trial (NCT03732677).

The trial, as he noted, yielded improved event-free survival (EFS) as well as overall survival (OS) with a treatment of gemcitabine (Gemzar) and cisplatin with durvalumab (Imfinzi) in patients with muscle-invasive bladder cancer (MIBC).

Additionally, reported data demonstrated that in the group of patients who didn’t undergo a pathologic complete response (pCR), the median EFS was 34.7 months (95% CI, 20.5-not reached [NR]) in the durvalumab arm vs 22.8 months (95% CI, 15.5-30.6) in the comparator arm (HR, 0.77; 95% CI, 0.631-0.948). The median OS was NR (95% CI, NR-NR) vs NR (95% CI, 53.9-NR), respectively (HR, 0.85; 95% CI, 0.660-1.068).

Sonpavde concluded by saying that he hopes that more attention is given to these treatments in MIBC.

Transcript:

The NIAGARA study is a landmark study, the first neoadjuvant phase 3 study showing improved survival—I will add not just EFS, but also OS in the context of neoadjuvant cisplatin-based combination chemotherapy. The level of increment in EFS and OS was approximately a 10% absolute benefit in long-term EFS and OS. It is on the level of improvement we saw with the neoadjuvant cisplatin-based chemotherapy compared with nothing in the neoadjuvant space. There are, of course, some toxicity issues with adding durvalumab, but, overall, the immune adverse effects seemed low in the 20% to 25% range. The gemcitabine/cisplatin/durvalumab [combination] deserves strong consideration in the neoadjuvant space. The EFS curve separated early, and even before or around the time of cystectomy. That suggests that there is an early benefit because the question that’s been asked is, “Is adding a PD-L1 inhibitor to neoadjuvant therapy necessary, or can we just do it adjuvantly like we’re doing with adjuvant nivolumab [Opdivo].” If you had early separation in curves for the EFS, that makes a strong case that starting the PD-1 inhibitor early in combination might be better. This whole issue needs to be looked at more. There’s not a trial that’s going to compare these 2 approaches, so, unfortunately, we’re going to be left with comparing across studies and perhaps some analyses in the real world in the future.

Reference

Galsky M, Van Der Heijden M, Catto J, et al. Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA. J Clin Oncol 43, 2025 (suppl 5; abstr 659). doi:10.1200/JCO.2025.43.5_suppl.659