Perioperative Durvalumab Boosts Survival in MIBC, Cutting Death Risk by 25%

Perioperative durvalumab, combined with chemotherapy and radical cystectomy, significantly improves survival outcomes in muscle-invasive bladder cancer (MIBC). The NIAGARA trial showed a 10% increase in pathological complete response (pCR) rates and a 25% reduction in death risk with durvalumab. These findings support durvalumab as a potential new standard of care for cisplatin-eligible MIBC patients.

Perioperative Durvalumab Boosts Survival in MIBC, Cutting Death Risk by 25%

The addition of perioperative durvalumab (Imfinzi) to standard chemotherapy has shown significant benefits in the treatment of muscle-invasive bladder cancer (MIBC), according to findings from the phase 3 NIAGARA trial (NCT03732677). Presented at the 2025 Genitourinary Cancers Symposium, these results indicate that durvalumab improves event-free survival (EFS), overall survival (OS), and metastasis-free survival, regardless of whether patients achieve a pathological complete response (pCR).

Key Findings from NIAGARA Trial

The NIAGARA trial demonstrated a 10% increase in pCR rate and a 25% reduction in the risk of death with durvalumab. The study involved patients with cisplatin-eligible MIBC who underwent radical cystectomy and adjuvant chemotherapy. Researchers found that perioperative durvalumab provided clinical benefits to patients both with and without a pCR, reinforcing its role as a potential new standard of care in this setting.

Improvements in Survival Outcomes

Dr. Matthew Galsky, a leading investigator in the study and a professor at The Tisch Cancer Institute, highlighted the significant impact of durvalumab in improving clinical outcomes. The primary endpoint analysis showed that perioperative durvalumab enhanced metastasis-free survival, with a hazard ratio (HR) of 0.67. At the 24-month mark, metastasis-free survival increased by 10% in the durvalumab-treated group compared to the control group. Disease-specific survival was also improved, with an HR of 0.69 favoring durvalumab.

The pCR rate was notably higher in the durvalumab arm (37.3%, 95% CI: 33.2-41.6) than in the comparator arm (27.5%, 95% CI: 23.8-31.6). Researchers also analyzed baseline characteristics of patients achieving and not achieving pCR and found no major differences between the two groups.

Patients who achieved a pCR had longer EFS compared to those who did not. However, the addition of perioperative durvalumab was linked to better EFS outcomes for both groups, with an HR of 0.58 for those achieving a pCR and an HR of 0.77 for those not achieving a pCR. Similarly, while patients with a pCR experienced longer OS, durvalumab improved OS trends for both pCR and non-pCR groups.

Prior Findings and Updated Data

Earlier results from the NIAGARA trial, presented at the 2024 European Society for Medical Oncology Congress, reported a significant EFS improvement, with an HR of 0.68 (95% CI: 0.56-0.82). The median follow-up was 42.3 months (range: 0.03-61.3 months). At two years, landmark EFS rates were 68% in the durvalumab arm compared to 60% in the comparator arm, representing an 8% increase.

Dr. Thomas B. Powles, who presented data at the 2024 ESMO Congress, emphasized the survival benefits, noting a 25% reduction in the risk of death. The durvalumab arm reported 136 deaths (25.5%) versus 169 deaths (31.9%) in the control group (HR: 0.75; 95% CI: 0.59-0.93; P = 0.0106), confirming statistical significance.

NIAGARA Trial Design and Patient Population

The trial enrolled adults with cisplatin-eligible MIBC (cT2-T4aN0/1M0) with confirmed urothelial carcinoma, including those with divergent differentiation or histologic subtypes. Patients needed to be eligible for radical cystectomy and have a creatinine clearance of at least 40 mL/min.

Participants were randomly assigned 1:1 to either a durvalumab-based regimen or a standard chemotherapy regimen. The durvalumab arm received 1500 mg durvalumab intravenously every three weeks, alongside gemcitabine and cisplatin for four cycles, followed by radical cystectomy and eight cycles of adjuvant durvalumab. The control group received four cycles of gemcitabine and cisplatin followed by radical cystectomy.

The trial’s primary endpoints were EFS and pCR, with OS as a key secondary endpoint. Other secondary endpoints included metastasis-free survival, disease-specific survival, and safety assessments. In a post hoc exploratory analysis, investigators evaluated EFS and OS based on pCR status.

Safety and Adverse Effects

The safety analysis showed that nearly all patients experienced some form of adverse event (AE). In the durvalumab arm, 99% (527 patients) reported AEs, while 100% (525 patients) in the comparator arm experienced AEs. Grade 3/4 AEs occurred in 69% (368 patients) of the durvalumab arm and 68% (355 patients) of the control arm.

Discontinuation of durvalumab due to AEs occurred in 9% (50 patients), while 14% (72 patients) discontinued neoadjuvant chemotherapy. In comparison, 15% (80 patients) in the control group discontinued chemotherapy. Surgery was delayed in 2% (9 patients) of the durvalumab arm and 1% (6 patients) of the control arm, while 1% of patients in both groups were unable to undergo radical cystectomy due to AEs. The incidence of grade 3-4 AEs was equal between treatment arms at 41%.

Immune-mediated AEs were observed in 21% of patients receiving durvalumab, primarily grade 1-2 events. The most common immune-related AE was hypothyroidism, occurring in 10% of durvalumab-treated patients. According to Dr. Galsky, these findings align with the known safety profile of durvalumab.

The Future of Immune Checkpoint Blockade in MIBC

Dr. Galsky underscored the significance of these results, stating that for decades, there had been no substantial advancements beyond neoadjuvant chemotherapy followed by radical cystectomy for MIBC patients. The success of immune checkpoint inhibitors, such as durvalumab, marks a turning point in treatment strategies.

The findings from the NIAGARA trial suggest that incorporating perioperative durvalumab into treatment regimens can enhance survival outcomes and provide new hope for patients with muscle-invasive bladder cancer. As further research progresses, this approach may become a standard therapeutic option for eligible patients.