{"entity":{"id":"paper-niagara-nejm-2024","kind":"paper","name":"NIAGARA: durvalumab before and after cystectomy for muscle-invasive bladder cancer","aka":[],"tldr":"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.\n\n24-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.","asOf":"2026-09-08","links":[{"label":"NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2408154"},{"label":"ClinicalTrials.gov NCT03732677","url":"https://clinicaltrials.gov/study/NCT03732677"}],"tags":[],"related":[],"cancers":["urothelial"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy","platinum"],"targets":["pdl1"],"drugs":["durvalumab"],"companies":["astrazeneca"],"institutions":["mount-sinai"],"pathways":[],"terms":["efs","pcr","neoadjuvant-adjuvant"],"trials":[],"people":["matthew-galsky"],"bottlenecks":["b-immunotherapy-response","b-trial-design","b-dormancy-mrd"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2408154","authors":"Powles T, Catto JWF, Galsky MD, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":1063},"route":"/key-papers/paper-niagara-nejm-2024/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"muscle-invasive-bladder-cancer","kind":"cancer","name":"Muscle-invasive and advanced bladder cancer","route":"/cancers/muscle-invasive-bladder-cancer/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"target":[{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"institution":[{"id":"mount-sinai","kind":"institution","name":"The Mount Sinai Hospital / Tisch Cancer Institute","route":"/institutions/mount-sinai/"}],"term":[{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"}],"person":[{"id":"matthew-galsky","kind":"person","name":"Matthew D. Galsky","route":"/people/matthew-galsky/"},{"id":"thomas-powles","kind":"person","name":"Thomas Powles","route":"/people/thomas-powles/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}