Clinical trialPhase 3Bladder cancer

Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer

N Engl J Med · 20241063 patients (533 durvalumab group, 530 comparator group)

Powles T, Catto JWF, Galsky MD, et al. N Engl J Med. 2024. 391:1773-1786

Study type: Clinical trial
Study name: NIAGARA
Phase: Phase 3
Design: Randomised, open-label, international multicentre trial (1:1 randomisation)
Sample size: 1063 patients (533 durvalumab group, 530 comparator group)
Source: N Engl J Med · 2024
Trial registration: NCT03732677

In plain words

In bladder cancer that has grown into the muscle layer, the standard treatment is several cycles of chemotherapy before surgery to remove the bladder. In the NIAGARA study, an immunotherapy drug called durvalumab was added to this chemotherapy and continued for several months after surgery. After two years, more patients were free of the cancer coming back (about 68 vs 60 out of every 100) and alive (about 82 vs 75 out of every 100), without more severe side effects overall and without delaying surgery. This treatment is for patients who can receive cisplatin.

Key results

67.8% vs 59.8%

24-month event-free survival

HR 0.68 (95% CI: 0.56 to 0.82); P<0.001

82.2% vs 75.2%

24-month overall survival

HR for death 0.75 (95% CI: 0.59 to 0.93); P=0.01

88.0% vs 83.2%

Radical cystectomy performed

40.6% vs 40.9%

Treatment-related grade 3 or 4 adverse events

Treatment-related deaths: 0.6% in each group

Drugs in this study:Cisplatin (Platinol)Gemcitabine (Gemzar)Durvalumab (Imfinzi)

Dose and schedule cards

Perioperative durvalumab + GC (NIAGARA)

Cisplatin-eligible MIBC cT2 to T4a N0/1 M0 (creatinine clearance ≥40 mL/min), ECOG 0 to 1, candidate for cystectomyOn the page “Bladder cancer” · Muscle-invasive cancer (MIBC): perioperative therapy and bladder preservation

Cisplatin-eligible MIBC cT2 to T4a N0/1 M0 (creatinine clearance ≥40 mL/min), ECOG 0 to 1, candidate for cystectomy

Drug	Dose	Route	Schedule
Neoadjuvant: 4 cycles of 21 days
Durvalumab	1500 mg	IV	Day 1
Cisplatin	70 mg/m² (creatinine clearance 40 to less than 60: 35 mg/m² on Days 1 and 8)	IV	Day 1
Gemcitabine	1000 mg/m²	IV	Days 1 and 8
Adjuvant after cystectomy
Durvalumab	1500 mg (body weight less than 30 kg: 20 mg/kg)	IV	Every 4 weeks, up to 8 cycles

Cycle length: Neoadjuvant every 21 days; adjuvant every 28 days
Duration: 4 cycles before surgery + up to 8 cycles after surgery

Per the FDA label and the FDA approval summary and the NIAGARA trial.

On the page “Bladder cancer” · Muscle-invasive cancer (MIBC): perioperative therapy and bladder preservation

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Durvalumab group

Neoadjuvant: durvalumab 1500 mg IV + gemcitabine 1000 mg/m² + cisplatin 70 mg/m², every 3 weeks for 4 cycles; with creatinine clearance 40 to less than 60 mL/min, split-dose cisplatin 35 mg/m² on days 1 and 8 of each cycle. Then radical cystectomy.

Adjuvant: durvalumab 1500 mg IV every 4 weeks alone for up to 8 cycles (weight under 30 kg: 20 mg/kg).

2Comparator group

Gemcitabine 1000 mg/m² + cisplatin 70 mg/m² every 3 weeks for 4 cycles (split-dose cisplatin 35 mg/m² on days 1 and 8 with clearance 40 to less than 60), then radical cystectomy without adjuvant treatment.

Source of the regimen details: FDA label for IMFINZI (DailyMed, Clinical Studies section, NIAGARA) and ClinicalTrials.gov NCT03732677

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults with operable muscle-invasive bladder cancer, clinical stage T2 to T4a, N0 or N1, without metastasis (M0), with urothelial (transitional cell) or mixed histology, who were eligible for cisplatin-based chemotherapy and scheduled for radical cystectomy; ECOG performance status zero or 1 and no prior systemic therapy for muscle-invasive disease (per ClinicalTrials.gov).

Endpoints

Primary endpoint: event-free survival (one of two primary endpoints; events included progression, recurrence, not undergoing radical cystectomy, or death from any cause). Key secondary endpoint: overall survival.

Safety and side effects

Treatment-related grade 3 or 4 adverse events occurred in 40.6% of the durvalumab group and 40.9% of the comparator group; deaths from treatment-related adverse events were 0.6% in each group. Adding durvalumab did not prevent surgery (cystectomy in 88.0% vs 83.2%).

Clinical significance and place in guidelines

NIAGARA was the first phase 3 trial to show an overall survival improvement in muscle-invasive bladder cancer by adding immunotherapy to neoadjuvant chemotherapy. On 28 March 2025 the FDA approved durvalumab with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment after radical cystectomy, for adults with muscle-invasive bladder cancer. According to the 2026 EAU guideline text, this regimen was also approved by the EMA in July 2025, and the EAU guideline recommends it for T2 to T4a, cN0 M0 patients eligible for cisplatin and immunotherapy.

Limitations

Open-label design (no placebo); the separate effects of the neoadjuvant and adjuvant durvalumab components cannot be distinguished; only cisplatin-eligible patients were enrolled; the comparator group did not receive adjuvant immunotherapy (such as nivolumab).

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.