Durvalumab Shows Improvement in EFS/OS for Muscle-Invasive Bladder Cancer

Durvalumab improved efficacy in patients with muscle-invasive bladder cancer.

Durvalumab (Imfinzi) plus chemotherapy portrayed a statistically significant and clinically meaningful improvement in event-free survival (EFS) and overall survival (OS) for patients with muscle-invasive bladder cancer (MIBC), according to results from the phase 3 NIAGARA trial (NCT03732677).¹

The trial compared the durvalumab combination against neoadjuvant chemotherapy. In the trial, patients were given durvalumab plus neoadjuvant chemotherapy before cystectomy followed by durvalumab monotherapy. The safety profile of durvalumab with chemotherapy was consistent with the safety profiles of the individual agents, and the addition of durvalumab did not increase the discontinuation of treatment due to adverse effect (AE), or compromise surgery completion compared with neoadjuvant chemotherapy alone.

Additional data will be presented at an upcoming medical meeting, and the results will be shared with regulatory authorities.

“Nearly half of patients with muscle-invasive bladder cancer who receive standard of care still experience disease recurrence or progression,” Thomas Powles, MD, professor and director of Barts Cancer Centre in London, and lead investigator in the trial, said in the press release. “These NIAGARA data show for the first time that adding durvalumab to chemotherapy before surgery followed by durvalumab extends patients’ lives.”

The press release also highlighted common severe and fatal immune-mediated AEs for use of durvalumab as a single agent and did not receive prior radiation included pneumonitis in 2.4% of patients with fatal occurring in less than 0.1%, and grade 3/4 in 0.4%. Additionally, colitis occurred in 2.4%, with less than .01% having grade 4 AEs, and 0.4% had grade 3; hepatitis occurred in 2.8%, 0.2% was fatal, 0.3% was grade 4 and 1.4% was grade 3.

The dual primary end points for the phase 3 trial are pathologic complete response (PCR) rates and EFS.² The secondary end points included EFS at 24 months, proportion of patients who underwent cystectomy, and overall survival rate at 5 years.

The phase 3, randomized, open-label, multi-center international study (n = 1063) included 2 arms: one experimental arm assessing chemotherapy in combination with durvalumab both prior to radical cystectomy and 8 cycles following surgery and 1 active comparator arm assessing chemotherapy alone.

Inclusion criteria include patients with resectable MIBC with clinical stage T2-T4aN0/1M0 with transitional and mixed transitional cell histology. Patients were also included if they were planning to undergo a radical cystectomy, have not received prior systemic chemotherapy or immunotherapy for the treatment of MIBC, had an ECOG performance status of 0 or 1, and had a life expectancy of at least 12 weeks at randomization.

Exclusion criteria include evidence of lymph node or metastatic disease at the time of screening, prior pelvic radiotherapy within 2 years of randomization to study, and prior exposure to immune-mediated therapy. Patients were also excluded if they had current or prior use of immunosuppressive medication within 14 days before the first dose of the investigational product, excluding intranasal, inhaled, topical steroids, or local steroid injections; receipt of live attenuated vaccine within 30 days prior to the first dose of treatment; uncontrolled intercurrent illness; or active infection including tuberculosis, hepatitis B and C, and human immunodeficiency.

“The NIAGARA results support our strategy to move immunotherapy to the early stages of cancer treatment. This perioperative regimen with [durvalumab] improved survival and reduced the rate at which patients experience disease recurrence or progression. We are eager to bring this regimen with the potential to transform the standard of care to patients as soon as possible,” concluded Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca.

References

1. IMFINZI® (durvalumab) demonstrated statistically significant and clinically meaningful improvement in event-free survival and overall survival for muscle-invasive bladder cancer in NIAGARA phase III trial. News Release. June 25, 2024. Accessed June 25, 2024. https://tinyurl.com/evcvsfx3
2. Powles T, Meeks J J, Galsky M D, et al. A phase III, randomized, open-label, multicenter, global study of efficacy and safety of durvalumab in combination with gemcitabine plus cisplatin for neoadjuvant treatment followed by durvalumab alone for adjuvant treatment in muscle-invasive bladder cancer (NIAGARA). J. Clin. Oncol. 2021;39(6). doi:10.1200/JCO.2021.39.6_suppl.TPS505