BARCELONA — In a result that’s likely to change how some bladder cancer patients get care, AstraZeneca said that its drug Imfinzi boosted patient survival alongside chemotherapy and surgery.
Two years after treatment with the drug, 82.2% of patients were alive, compared with 75.2% of patients who didn’t get the immunotherapy (p=0.01), one of the trial’s secondary endpoints.
Sunil Verma“This is the first study of immunotherapy in bladder cancer with this perioperative approach, and the first study to show a statistically significant and clinically meaningful improvement in overall survival,” AstraZeneca’s global head of oncology, medical Sunil Verma told Endpoints News. “Given the magnitude of benefit, I think this has the potential to be practice-changing.”
AstraZeneca previously teased positive results from the trial, called NIAGARA, in June. The updated data were presented Sunday at the European Society for Medical Oncology meeting in Barcelona and also published in the New England Journal of Medicine.
The study examined patients with muscle-invasive bladder cancers, and one of the two primary endpoints was event-free survival at 24 months. In the group of patients who got Imfinzi, 67.8% hit that goal, compared with 59.8% in the control arm (p<0.001).
The NIAGARA trial divided the patients into two groups. The first was dosed with Imfinzi and the chemotherapy duo of gemcitabine and cisplatin, and they then went through surgery to remove their bladder and had adjuvant Imfinzi. The other group was only given neoadjuvant chemotherapy and then had the surgery.
In the trial, 417 of 530 participants (78.7%) in the Imfinzi group completed neoadjuvant treatment, compared with 389 of 526 patients (74%) in the control arm. Adverse events were the main reason for discontinuation and were roughly even between the two groups.
The study’s second primary endpoint was pathologic complete response. On that measure, Imfinzi didn’t show a statistically significant difference between the two groups.
But NIAGARA investigator Thomas Powles told delegates at the meeting that in a reanalysis, there was a “nominal statistical significance” favoring the Imfinzi arm.
Hints of strongest impact
One weakness of the trial was that it wasn’t designed to distinguish which part of the Imfinzi treatment — before or after surgery — had the most impact.
But researchers noted the Kaplan-Meier curve in the positive event-free survival endpoint diverged early — a possible indication that Imfinzi adds value before surgery. But they did caveat that NIAGARA was designed to study the “totality” of Imfinzi’s impact and not to distinguish how the neoadjuvant and adjuvant stages compared with each other.
It wasn’t the first time those questions have come up for the drug. In July, an FDA advisory committee reviewed the use of Imfinzi in conjunction with surgery in non-small cell lung cancer patients. At the hearing, committee members raised questions about how that trial, called AEGEAN, wasn’t designed to answer this question. Imfinzi was nonetheless approved for the disease in August.
Verma said that the FDA is likely to seek such data in future studies but not in completed ones such as NIAGARA. “We will certainly be submitting this package as a full treatment protocol for approval,” he added.
Imfinzi was already in the US bladder cancer market but was discontinued a few years later. In 2017, the immunotherapy was handed an FDA accelerated approval in certain urothelial carcinoma patients but was withdrawn in 2021 when the confirmatory trial DANUBE failed.