AstraZeneca aims to widen the pool of bladder cancer patients who can be treated with its PD-L1 inhibitor Imfinzi after the drug demonstrated benefits in those with a higher-risk form of non-muscle-invasive bladder cancer (NMIBC).
In the company’s POTOMAC phase 3 study, patients with high-risk NMIBC who were treated with Imfinzi for one year—along with standard-of-care Bacillus Calmette-Guérin (BCG) induction and maintenance therapy—experienced a statistically significant and clinically meaningful improvement in disease-free survival compared with those who received BCG induction and maintenance therapy alone, the company said.
The disease-free survival measure was defined as the time from study randomization to the first recurrence of high-risk disease or death from any cause.
A second experimental POTOMAC arm, however, did not reach statistical significance on the same endpoint, AstraZeneca said. That cohort weighed Imfinzi plus BCG without maintenance therapy against BCG induction and maintenance doses.
The trial was “not statistically powered” to “formally test” overall survival, AZ added, but a descriptive analysis “demonstrated no detriment" for the Imfinzi arm.
Still, an improvement in disease-free survival is significant for the patient group, considering that 80% of those with NMIBC “see their disease return” and nearly half may require bladder-removal surgery, principal trial investigator Maria De Santis, M.D., highlighted in AZ's press release.
Diagnoses of NMIBC, an early-stage form of bladder cancer, comprise more than 70% of all bladder cancer cases. About half of patients diagnosed with NMIBC are classified as high-risk for disease progression or recurrence.
The new Imfinzi trial results “represent a significant advance that will potentially allow more patients with early-stage bladder cancer to benefit from this important immunotherapy,” AstraZeneca’s chief medical officer and oncology chief development officer, Cristian Massacesi, said in a statement.
The company will share the data with global regulatory authorities and present the results at an upcoming medical meeting.
Earlier this year, AstraZeneca took Imfinzi to new heights in muscle-invasive bladder cancer (MIBC) with an FDA nod that made it the first immunotherapy cleared to treat patients both before and after surgery. In the company’s phase 3 NIAGARA trial, which supported the approval, an Imfinzi plus chemotherapy regimen showed a 32% reduction in the risk of a basket of negative events, including failure to move on to surgery, disease progression, recurrence or death, compared with chemotherapy alone.
The drug also reduced the risk of death by 25% in that study, representing the first PD-1/L1 inhibitor to deliver a survival win for MIBC patients.
Meanwhile, Pfizer recently tested its subcutaneous PD-1 inhibitor sasanlimab in the same high-risk population, finding that its offering beat standard of care in event-free survival. While the trial missed the mark on secondary endpoints, the primary win prompted Pfizer to pursue an FDA approval.
As for AZ's drug, Imfinzi is being studied across early and late-stage bladder cancer through various treatment combinations, including in patients with MIBC who can’t or won’t take cisplatin chemotherapy and in locally advanced or metastatic disease. The drug has collected several approvals across cancer types since its original 2017 nod, including in non-small cell lung cancer, limited-stage small cell lung cancer, biliary tract cancer and endometrial cancer, among others.