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