# NIAGARA: durvalumab before and after cystectomy for muscle-invasive bladder cancer

Source: https://onco.cc/key-papers/paper-niagara-nejm-2024/  
OnCo record `paper-niagara-nejm-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding the immunotherapy durvalumab to chemotherapy before bladder removal, and continuing it afterwards, reduced relapse and death in muscle-invasive bladder cancer, the first improvement on neoadjuvant chemotherapy in two decades.

## Summary

Open-label phase 3 trial of 1,063 patients with cisplatin-eligible muscle-invasive bladder cancer randomised to neoadjuvant gemcitabine-cisplatin with or without durvalumab, followed by radical cystectomy and, in the durvalumab arm, eight cycles of adjuvant durvalumab. Primary endpoints were event-free survival and pathological complete response.

24-month EFS was 67.8% vs 59.8% (HR 0.68) and 24-month OS 82.2% vs 75.2% (HR 0.75); pCR was 37.3% vs 27.5%. It made perioperative durvalumab a new standard for cisplatin-eligible patients and, following CheckMate 274 (adjuvant nivolumab), completed the move of checkpoint inhibitors into curative-intent bladder cancer treatment.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2024
- DOI: 10.1056/NEJMoa2408154
- Authors: Powles T, Catto JWF, Galsky MD, et al.
- Findings: 24-month event-free survival 67.8% vs 59.8%; HR 0.68 (95% CI 0.56-0.82).; 24-month overall survival 82.2% vs 75.2%; HR 0.75 (95% CI 0.59-0.93).; Pathological complete response 37.3% vs 27.5% (the pCR endpoint narrowly missed statistical significance in the initial analysis but was significant on re-analysis of all patients).; Cystectomy was performed in 88% of both arms; durvalumab did not delay surgery or increase surgical complications.; Grade 3-4 treatment-related adverse events about 41% in both arms.
- What it means: Patients fit enough for cisplatin whose bladder cancer has invaded the muscle wall should now be offered durvalumab with their pre-operative chemotherapy and for about a year after surgery, which improves the chance of cure without compromising the operation. The trial cannot say whether the adjuvant phase is necessary, or how to treat cisplatin-ineligible patients, for whom other trials are ongoing.
- Caveats: Open-label; the contribution of the adjuvant phase versus the neoadjuvant phase is not separable.; Cisplatin-ineligible patients (about half of real-world patients) were excluded.; Absolute EFS gain of about 8 points at two years; longer follow-up is needed.; Overlaps with adjuvant nivolumab (CheckMate 274) for patients with residual disease; sequencing is undefined.

## Sources

- NEJM 2024: https://doi.org/10.1056/NEJMoa2408154
- ClinicalTrials.gov NCT03732677: https://clinicaltrials.gov/study/NCT03732677

## Connected records

- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Muscle-invasive and advanced bladder cancer](https://onco.cc/cancers/muscle-invasive-bladder-cancer/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Platinum agents](https://onco.cc/technologies/platinum/)
- targets: [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Durvalumab](https://onco.cc/drugs/durvalumab/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/)
- institutions: [The Mount Sinai Hospital / Tisch Cancer Institute](https://onco.cc/institutions/mount-sinai/)
- terms: [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/)
- people: [Matthew D. Galsky](https://onco.cc/people/matthew-galsky/), [Thomas Powles](https://onco.cc/people/thomas-powles/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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