Muscle-invasive bladder cancer (MIBC) presents a significant clinical challenge, with nearly half of patients experiencing relapse after radical cystectomy, even following standard neoadjuvant chemotherapy.¹ This highlights an unmet need for effective treatment options in this patient population, particularly for those with resectable disease.¹ Recently, the European Commission (EC) has approved durvalumab, an anti-PD-L1 monoclonal antibody, in combination with gemcitabine and cisplatin as neoadjuvant therapy, followed by durvalumab monotherapy after surgery.² This approval marks durvalumab as the first perioperative immunotherapy authorized for resectable MIBC in the European Union (EU), supported by data from the global NIAGARA trial, which demonstrated a substantial reduction in recurrence rates and significant improvements in survival compared to neoadjuvant chemotherapy alone.¹

MIBC accounts for approximately 25% of bladder cancer cases, which is the ninth most common cancer globally.^3,4 Current treatment standards for cisplatin-eligible patients involve neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy with pelvic lymph node dissection. However, recurrence remains prevalent, occurring in 20%-30% of patients with pathologic stage pT2, around 40% in pT3, over 50% in pT4, and approximately 70% in node-positive disease.^1,3 Most relapses occur within two to three years, and existing systemic therapies rarely lead to a cure after recurrence.³

Durvalumab enhances anti-tumor immunity by selectively inhibiting PD-L1 from binding to its receptors, PD-1 and CD80.² The phase 3 NIAGARA trial enrolled 1,063 patients with histologically or cytologically confirmed MIBC (stage T2-T4a, N0-N1, M0) who were fit for cisplatin-based chemotherapy and cystectomy, and had not received prior systemic therapy.¹ Participants were randomized 1:1 to receive either durvalumab combined with neoadjuvant chemotherapy followed by adjuvant durvalumab (n=533) or standard neoadjuvant chemotherapy and cystectomy alone (n=530).¹

In the durvalumab arm, treatment included four cycles of durvalumab (1,500mg every 3 weeks) with gemcitabine (1,000mg/m² on days 1 and 8) and cisplatin (70mg/m² on day 1), followed by cystectomy and up to eight cycles of durvalumab (1,500mg every 4 weeks). The control arm received standard gemcitabine–cisplatin chemotherapy followed by cystectomy without adjuvant therapy.¹ The dual primary endpoints were event-free survival (EFS) and pathological complete response, with overall survival (OS) and safety as key secondary endpoints.¹

With a median follow-up of 42.3 months, the 24-month EFS was 67.8% for durvalumab vs. 59.8% for the control group, resulting in a 32% reduction in the risk of progression, recurrence, surgery omission, or death (HR=0.68, 95% CI: 0.56-0.82; p<0.0001).¹ Median EFS was not reached in the durvalumab group, while it was 46 months in the control group.¹ Furthermore, OS rates were superior in the intention-to-treat population, with 24-month OS rates of 82.2% vs. 75.2% (HR=0.75, 95% CI: 0.59-0.93; p=0.01).¹ 

The safety profile of perioperative durvalumab combined with neoadjuvant gemcitabine-cisplatin was consistent with the known profiles of the individual agents.¹ Treatment-related adverse events (AEs) of any grade occurred in 94.7% of patients receiving durvalumab compared to 92.6% in the control group, with grade 3/4 events reported in 40.6% and 40.9%, respectively.¹ Immune-related AEs were consistent with the known profile of durvalumab, occurring in 20.9% of patients in the durvalumab arm vs. 3.0% in the control arm.¹ The most common immune-mediated AEs (≥1%) in the durvalumab group included hypothyroidism (10.4%), hyperthyroidism (2.5%), dermatitis/rash (2.3%), renal events (1.7%), diarrhea/colitis (1.5%), and pneumonitis (1.3%).¹ No new safety signals were identified in either the neoadjuvant or adjuvant settings.¹ 

In summary, the EC approval of durvalumab as a perioperative therapy for resectable MIBC represents a significant advancement in the treatment landscape, offering a long-awaited opportunity to reduce recurrence and improve survival. This approval expands the role of immunotherapy and provides new hope for patients with MIBC.^1,2