The result comes months after an FDA advisory committee flagged the risk of potential overtreatment with perioperative regimens.
A perioperative regimen of PD-L1 blocker Imfinzi yielded “clinically meaningful” survival benefits for patients with muscle-invasive bladder cancer, AstraZeneca announced Sunday.
The readout comes from the Phase III NIAGARA study, which tested an investigational perioperative regimen of Imfinzi (durvalumab) with chemotherapy before cystectomy, followed by Imfinzi after surgery. As a comparator, AstraZeneca used neoadjuvant chemotherapy followed by radical cystectomy. NIAGARA’s primary endpoint is event-free survival (EFS) and a key secondary endpoint is overall survival (OS).
Results, which were presented at the 2024 European Society for Medical Oncology Congress (ESMO 2024), showed that the perioperative schedule resulted in a 32% drop in the risk of disease progression, recurrence, not undergoing surgery or death. This effect was statistically significant, with a p-value less than 0.0001. At the time of the analysis, estimated EFS was not yet reached in patients on the Imfinzi regimen versus 46.1 months in comparators.
At two years, 67.8% of Imfinzi-treated patients were event-free, as opposed to 59.8% of patients in the comparator arm. OS was also better after treatment with the Imfinzi regimen, which significantly reduced the risk of death by 25% versus radical cystectomy with neoadjuvant chemotherapy.
NIAGARA found the perioperative Imfinzi regimen to be well-tolerated with no new safety signals. Adding Imfinzi to neoadjuvant chemotherapy did not impair patients’ ability to complete surgery versus neoadjuvant treatment alone, according to AstraZeneca’s news release.
Susan Galbraith, AstraZeneca’s executive vice president of Oncology R&D, said in a statement said that the NIAGARA data showed perioperative Imfinzi can elicit “compelling improvements” in muscle-invasive bladder cancer.
“This is the first immunotherapy regimen to significantly extend overall survival in muscle-invasive bladder cancer, and it further validates our strategy to move cancer treatment as early as possible to maximize benefit for patients,” Galbraith added.
However, Sunday’s readout comes as the FDA appears to be rethinking its position on perioperative treatment in cancer. AstraZeneca’s previous Imfinzi application—which proposed a perioperative regimen in non-small cell lung cancer (NSCLC)—prompted the agency to convene its Oncologic Drugs Advisory Committee to assess the risk/benefit tradeoff of this treatment schedule.
In a briefing document ahead of the panel meeting, the FDA flagged the “potential overtreatment” of patients given the PD-L1 therapy both before and after surgery, in turn exposing them to an excessive burden of adverse events.
The advisory committee agreed with the FDA. Though it recommended against asking the company to run another study—citing practicality matters and the urgent need for treatments in this space—the external experts unanimously agreed that there is a strong need to change trial designs in perioperative NSCLC to specifically delineate which phase of treatment is contributing what therapeutic effect. It is not yet known what these design changes will be and if they will apply to other cancer indications.
