The National Institute for Health and Care Excellence (NICE) has issued final draft guidance recommending durvalumab (Imfinzi, AstraZeneca), given with gemcitabine and cisplatin before surgery and continued as monotherapy afterwards, for adults with resectable muscle-invasive bladder cancer (MIBC). 

The decision marks the first time immunotherapy has been incorporated into both the neoadjuvant (pre-surgical) and adjuvant (post-surgical) stages of treatment for this form of bladder cancer.

Under the recommended regimen, durvalumab is administered alongside chemotherapy before radical cystectomy and continued after surgery. The perioperative approach aims to reduce the risk for recurrence and improve long-term survival.

Understanding the Clinical Challenge

MIBC is characterised by malignancy that has spread into the bladder's muscle layer without distant metastases. In England, 18,060 new bladder cancer cases were diagnosed in 2022. The disease predominantly affects people in their sixties and seventies, although younger individuals can also be affected. Men are affected more frequently than women. 

Approximately 630 patients per year are expected to be eligible for this therapy. 

Symptoms may include haematuria, lower back or abdominal pain, and unexplained weight loss. Despite current standard care, around half of patients experience recurrence or progression within 5 years.

A New Standard in Perioperative Care

Durvalumab is a human monoclonal antibody targeting the PD-L1 protein, blocking its interactions with PD-1 and CD80 receptors. This mechanism enables the immune system to recognise and attack cancer cells more effectively.

The perioperative protocol involves administering durvalumab by infusion every 3 weeks alongside chemotherapy before surgery, followed by administration every 4 weeks as monotherapy after radical cystectomy, in line with its marketing authorisation.

“This positive NICE recommendation marks an important step forward for people living with one of the most aggressive forms of bladder cancer,” said Tom Keith-Roach, country president of AstraZeneca UK.

Proven Survival and Progression Benefits

The recommendation is based on evidence from the phase 3 NIAGARA trial, which enrolled 1063 patients with MIBC. The study randomised 533 patients to receive durvalumab plus neoadjuvant chemotherapy (gemcitabine and cisplatin) followed by durvalumab monotherapy, while 530 patients received neoadjuvant chemotherapy alone.

The durvalumab regimen demonstrated a 32% reduction in the risk for progression compared with standard care. At 24 months, overall survival was 82.2% in the durvalumab group vs 75.2% in the chemotherapy-only group. Event-free survival at 24 months was 67.8% with durvalumab compared with 59.8% in the control arm.

Radical cystectomy was performed in 88.0% of patients in the durvalumab group compared with 83.2% in the control group. 

Rates of grade 3 or 4 adverse events were similar between groups (69.4% vs 67.5%).

Cost and Access

NICE concluded that despite uncertainty in long-term modelling and indirect comparisons, the most plausible incremental cost-effectiveness ratio falls within the range considered an acceptable use of NHS resources.

Durvalumab will be available to the NHS through a confidential commercial access agreement. The list price is £592.00 per 2.4-mL vial and £2,466.00 per 10-mL vial, although the agreed NHS discount remains confidential. 

Under the guidance, NHS England and integrated care boards must fund the treatment within 90 days of final publication. 

Interim funding will be available through the Cancer Drugs Fund from the point of marketing authorisation or the release of positive draft guidance, whichever occurs later, before transitioning to routine commissioning.