AZ cues up broader use of Imfinzi in bladder cancer

Bladder cancer has been billed by AstraZeneca as a key growth area for its immunotherapy Imfinzi, an ambition that has now been buoyed by the results of the VOLGA trial.

VOLGA was conducted in patients with muscle-invasive bladder cancer (MIBC) who are ineligible or refuse to take platinum-based chemotherapy, and builds on the approval last year of PD-L1 inhibitor Imfinzi (durvalumab) as a peri-operative regimen for MIBC in combination with platinum chemo, based on the NIAGRA trial.

The new study showed that giving Imfinzi alongside Pfizer and Astellas's Nectin-4-targeting Padcev (enfortumab vedotin) – once again before and after surgery to remove the tumour – significantly extended both event-free survival (EFS) and overall survival (OS) compared to standard therapy based on surgery to remove the bladder altogether.

Results from an arm combining Imfinzi with AZ's CTLA4 inhibitor Imjudo (tremelimumab) and Padcev were less impressive, showing a significant improvement in EFS but only a trend towards improved OS. The reasons for the disparity will no doubt be scrutinised when the full dataset is presented at a future oncology meeting.

Bladder cancer has been billed by AZ as a "meaningful new opportunity" for Imfinzi, which brought in more than $6 billion in sales for AZ last year. a 37% increase driven by strong take-up in bladder and gastric/gastroesophageal junction cancers alongside established use in lung, liver, endometrial, and biliary tract tumours.

Imfinzi's approval last year as a peri-operative regimen for MIBC – where the tumour invades the muscle wall of the bladder, without distant metastases – was the first for a cancer immunotherapy in that setting, although Bristol Myers Squibb's PD-1 inhibitor Opdivo (nivolumab) has been cleared for use as a post-surgery option for MIBC tumours that express the PD-L1 biomarker at a level of 1% or more.

Around a quarter of bladder cancer cases come under the MIBC category, and of these, up to half of patients are ineligible for cisplatin-based chemotherapy due to impaired renal function or other medical conditions and have generally had surgery to remove the bladder. Despite that radical treatment, they tend to be at an elevated risk of cancer recurrence.

VOLGA is now the third positive phase 3 readout for Imfinzi in bladder cancer, after NIAGARA and the POTOMAC study in non-muscle invasive bladder cancer (NMIBC), which showed that giving the PD-L1 inhibitor with standard BCG treatment was more effective than BCG alone in improving disease-free survival (DFS). The NMIBC indication is currently under regulatory review.

AZ's head of oncology and haematology R&D, Susan Galbraith, said the three studies have set "a strong foundation for Imfinzi as the immunotherapy backbone in this early-stage, curative-intent setting."

Imfinzi was granted accelerated approval in previously treated adults with locally advanced or metastatic forms of bladder cancer in 2017, but that was subsequently withdrawn after the failure of a confirmatory study. AZ is now running another phase 3 trial – NILE – to try to resurrect use of the drug in patients with more advanced-stage disease.