AstraZeneca Withdraws U.S. Use of Imfinzi as Advanced Bladder Cancer Treatment

Imfinzi withdrawn by AstraZeneca. (Bodo Marks/picture alliance via Getty Images)

AstraZeneca will voluntarily withdraw the use of its checkpoint inhibitor Imfinzi (durvalumab) as a treatment for bladder cancer in the United States following a failure to meet endpoints in a post-approval clinical study.

The U.K.-based pharma giant said the decision was made in collaboration with the U.S. Food and Drug Administration (FDA) after the Phase III DANUBE study missed the mark of improving overall survival in patients with advanced bladder cancer who have previously been treated with platinum-containing chemotherapy. In 2017, the FDA authorized Imfinzi for this indication under accelerated approval contingent upon results of the Phase III DANUBE study in the first-line setting. However, in March of 2020, the company announced that study failed to meet endpoints.

In that study, Imfinzi was being assessed as a standalone treatment, as well as in combination with tremelimumab, an anti-CTLA4 antibody. The combination of Imfinzi and tremelimumab was being tested in patients regardless of their PD-L1 expression. Both approaches failed to improve overall survival in patients with this advanced form of bladder cancer.

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumor's immune-evading tactics and releasing the inhibition of immune responses. PD-L1 is widely expressed in tumor and immune cells in patients with bladder cancer and helps tumors evade detection from the immune system. 

Dave Fredrickson, executive vice president of AstraZeneca’s Oncology Business Unit, said the withdrawal of Imfinzi in this indication is disappointing, but noted the company respect the “principles FDA set out when the accelerated approval pathway was founded.” He said the company remains committed to bringing new and innovative options to cancer patients.

“The science of immunotherapy has moved swiftly over the past few years, bringing new options to patients at an unprecedented pace,” Fredrickson said in a statement. “In the last three years, Imfinzi has become an important standard of care in multiple lung cancer settings, an area of considerable focus for AstraZeneca.”

AstraZeneca said the withdrawal of Imfinzi in this indication is aligned with FDA guidance for evaluating indications with accelerated approvals that did not meet post-marketing requirements, as part of a broader industry-wide evaluation. 

This withdrawal does not impact the use of Imfinzi for this indication outside the United States. Healthcare providers are being notified of this update. Patients with metastatic bladder cancer currently being treated with Imfinzi should consult with their healthcare provider regarding their ongoing care, the company said.

In the U.S., Imfinzi has been approved for non-small cell lung cancer, extensive-stage small cell lung cancer. Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.

The announced withdrawal comes hard on the heels of Imfinzi’s failure to improve overall survival in patients with metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors expressed high levels of PD-L1. In the Phase III KESTREL study, Imfinzi failed in comparison to the EXTREME treatment regimen, which was chemotherapy plus cetuximab, a standard of care.